5429 lines
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- *602700 - E1A-BINDING PROTEIN, 300-KD; EP300
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*602700</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/602700">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000100393;t=ENST00000263253" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=2033" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602700" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000100393;t=ENST00000263253" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001362843,NM_001429" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001429" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=602700" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=04078&isoform_id=04078_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/EP300" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/495301,31753089,50345997,77998117,119580812,134274224,223590203,1384865987,1876576070,1876576072,1876576074,1876576076,1876576078,1876576080,1876576082,1876576084,1876576086,1876576088,1876576090,1876576092,1876576094,1876576096,1876576098,1876576100,1876576102,1876576104" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q09472" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=2033" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000100393;t=ENST00000263253" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=EP300" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=EP300" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+2033" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/EP300" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:2033" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2033" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr22&hgg_gene=ENST00000263253.9&hgg_start=41092592&hgg_end=41180077&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3373" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3373" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ep300" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602700[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602700[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/EP300/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000100393" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=EP300" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=EP300" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=EP300" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/EP300" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=EP300&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA27807" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:3373" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0261617.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1276116" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/EP300#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1276116" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2033/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=2033" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000366;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-080403-15" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2033" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=EP300&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
|
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602700
|
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
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<span class="mim-font">
|
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E1A-BINDING PROTEIN, 300-KD; EP300
|
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
p300
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=EP300" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EP300</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/22/315?start=-3&limit=10&highlight=315">22q13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr22:41092592-41180077&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">22:41,092,592-41,180,077</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=114500,618333,613684" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/22/315?start=-3&limit=10&highlight=315">
|
|
22q13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Colorectal cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/114500"> 114500 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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|
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|
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</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Menke-Hennekam syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618333"> 618333 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>The EP300 gene encodes p300, a histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation (<a href="#12" class="mim-tip-reference" title="Gayther, S. A., Batley, S. J., Linger, L., Bannister, A., Thorpe, K., Chin, S.-F., Daigo, Y., Russell, P., Wilson, A., Sowter, H. M., Delhanty, J. D. A., Ponder, B. A. J., Kouzarides, T., Caldas, C. <strong>Mutations truncating the EP300 acetylase in human cancers.</strong> Nature Genet. 24: 300-303, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700188</a>] [<a href="https://doi.org/10.1038/73536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700188">Gayther et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability to interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. <a href="#7" class="mim-tip-reference" title="Eckner, R., Ewen, M. E., Newsome, D., Gerdes, M., DeCaprio, J. A., Lawrence, J. B., Livingston, D. M. <strong>Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.</strong> Genes Dev. 8: 869-884, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7523245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7523245</a>] [<a href="https://doi.org/10.1101/gad.8.8.869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7523245">Eckner et al. (1994)</a> isolated a cDNA encoding full-length human p300. p300 contains 3 cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. p300 and CREB-binding protein (CREBBP, or CBP; <a href="/entry/600140">600140</a>) are highly related in primary structure (<a href="#3" class="mim-tip-reference" title="Arany, Z., Sellers, W. R., Livingston, D. M., Eckner, R. <strong>E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. (Letter)</strong> Cell 77: 799-800, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8004670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8004670</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90127-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8004670">Arany et al., 1994</a>). Several protein motifs such as a bromodomain, a KIX domain, and 3 regions rich in cys/his residues are well conserved between these 2 proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7523245+8004670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Nibbeling, E. A. R., Duarri, A., Verschuuren-Bemelmans, C. C., Fokkens, M. R., Karjalainen, J. M., Smeets, C. J. L. M., de Boer-Bergsma, J. J., van der Vries, G., Dooijes, D., Bampi, G. B., van Diemen, C., Brunt, E., and 9 others. <strong>Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.</strong> Brain 140: 2860-2878, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29053796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29053796</a>] [<a href="https://doi.org/10.1093/brain/awx251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29053796">Nibbeling et al. (2017)</a> noted that EP300 is strongly expressed in human cerebellum as well as in other brain regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29053796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#21" class="mim-tip-reference" title="Lin, C. H., Hare, B. J., Wagner, G., Harrison, S. C., Maniatis, T., Fraenkel, E. <strong>A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies.</strong> Molec. Cell 8: 581-590, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11583620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11583620</a>] [<a href="https://doi.org/10.1016/s1097-2765(01)00333-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11583620">Lin et al. (2001)</a> identified a compactly folded 46-residue domain in CBP and p300, the IRF3-binding domain (IBID), and determined its structure by nuclear magnetic resonance spectroscopy. IBID has a helical framework containing an apparently flexible polyglutamine loop that participates in ligand binding. Spectroscopic data indicated that induced folding accompanies association of IBID with its partners, which exhibit no evident sequence similarities. IBID is an important contributor to signal integration by CBP and p300. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11583620" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Crystal Structure</em></strong></p><p>
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<a href="#23" class="mim-tip-reference" title="Liu, X., Wang, L., Zhao, K., Thompson, P. R., Hwang, Y., Marmorstein, R., Cole, P. A. <strong>The structural basis of protein acetylation by the p300/CBP transcriptional coactivator.</strong> Nature 451: 846-850, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18273021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18273021</a>] [<a href="https://doi.org/10.1038/nature06546" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18273021">Liu et al. (2008)</a> described a high resolution x-ray crystal structure of a semisynthetic heterodimeric p300 HAT domain in complex with a bisubstrate inhibitor, Lys-CoA. This structure showed that p300/CBP is a distant cousin of other structurally characterized HATs, but revealed several novel features that explain the broad substrate specificity and preference for nearby basic residues. Based on this structure and accompanying biochemical data, <a href="#23" class="mim-tip-reference" title="Liu, X., Wang, L., Zhao, K., Thompson, P. R., Hwang, Y., Marmorstein, R., Cole, P. A. <strong>The structural basis of protein acetylation by the p300/CBP transcriptional coactivator.</strong> Nature 451: 846-850, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18273021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18273021</a>] [<a href="https://doi.org/10.1038/nature06546" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18273021">Liu et al. (2008)</a> proposed that p300/CBP uses an unusual hit-and-run (Theorell-Chance) catalytic mechanism that is distinct from other characterized HATs. Several disease-associated mutations could also be readily accounted for by the p300 HAT structure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18273021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Ortega, E., Rengachari, S., Ibrahim, Z., Hoghoughi, N., Gaucher, J., Holehouse, A. S., Khochbin, S., Panne, D. <strong>Transcription factor dimerization activates the p300 acetyltransferase.</strong> Nature 562: 538-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-018-0621-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30323286">Ortega et al. (2018)</a> described a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighboring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. <a href="#29" class="mim-tip-reference" title="Ortega, E., Rengachari, S., Ibrahim, Z., Hoghoughi, N., Gaucher, J., Holehouse, A. S., Khochbin, S., Panne, D. <strong>Transcription factor dimerization activates the p300 acetyltransferase.</strong> Nature 562: 538-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-018-0621-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30323286">Ortega et al. (2018)</a> concluded that their data explained how cellular signaling and the activation and dimerization of transcription factors control the activation of p300, and therefore explained why gene transcription is associated with chromatin acetylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30323286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Eckner, R., Ewen, M. E., Newsome, D., Gerdes, M., DeCaprio, J. A., Lawrence, J. B., Livingston, D. M. <strong>Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.</strong> Genes Dev. 8: 869-884, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7523245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7523245</a>] [<a href="https://doi.org/10.1101/gad.8.8.869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7523245">Eckner et al. (1994)</a> examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. They showed that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7523245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Weaver, B. K., Kumar, K. P., Reich, N. C. <strong>Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1.</strong> Molec. Cell. Biol. 18: 1359-1368, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9488451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9488451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9488451[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.18.3.1359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9488451">Weaver et al. (1998)</a> identified EP300/CREBBP and IRF3 (<a href="/entry/603734">603734</a>) as components of DRAF1 (double-stranded RNA-activated factor-1), a positive regulator of interferon-stimulated gene transcription that functions as a direct response to viral infection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9488451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The cytokines LIF (<a href="/entry/159540">159540</a>) and BMP2 (<a href="/entry/112261">112261</a>) signal through different receptors and transcription factors, namely STATs and SMADs, respectively. <a href="#27" class="mim-tip-reference" title="Nakashima, K., Yanagisawa, M., Arakawa, H., Kimura, N., Hisatsune, T., Kawabata, M., Miyazono, K., Taga, T. <strong>Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.</strong> Science 284: 479-482, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205054</a>] [<a href="https://doi.org/10.1126/science.284.5413.479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205054">Nakashima et al. (1999)</a> found that LIF and BMP2 act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacted physically with STAT3 (<a href="/entry/102582">102582</a>) at its amino terminus in a cytokine stimulation-independent manner, and with SMAD1 (<a href="/entry/601595">601595</a>) at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and SMAD1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neuronal progenitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205054" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Hasan, S., Hassa, P. O., Imhof, R., Hottiger, M. O. <strong>Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis.</strong> Nature 410: 387-391, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11268218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11268218</a>] [<a href="https://doi.org/10.1038/35066610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11268218">Hasan et al. (2001)</a> demonstrated that p300 may have a role in DNA repair synthesis through its interaction with proliferating cell nuclear antigen (PCNA; <a href="/entry/176740">176740</a>). <a href="#16" class="mim-tip-reference" title="Hasan, S., Hassa, P. O., Imhof, R., Hottiger, M. O. <strong>Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis.</strong> Nature 410: 387-391, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11268218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11268218</a>] [<a href="https://doi.org/10.1038/35066610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11268218">Hasan et al. (2001)</a> demonstrated that in vitro and in vivo p300 forms a complex with PCNA that does not depend on the S phase of the cell cycle. A large fraction of both p300 and PCNA colocalized to speckled structures in the nucleus. Furthermore, the endogenous p300-PCNA complex stimulates DNA synthesis in vitro. Chromatin immunoprecipitation experiments indicated that p300 is associated with freshly synthesized DNA after ultraviolet irradiation. <a href="#16" class="mim-tip-reference" title="Hasan, S., Hassa, P. O., Imhof, R., Hottiger, M. O. <strong>Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis.</strong> Nature 410: 387-391, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11268218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11268218</a>] [<a href="https://doi.org/10.1038/35066610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11268218">Hasan et al. (2001)</a> suggested the p300 may participate in chromatin remodeling at DNA lesion sites to facilitate PCNA function in DNA repair synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11268218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Hasan, S., Stucki, M., Hassa, P. O., Imhof, R., Gehrig, P., Hunziker, P., Hubscher, U., Hottiger, M. O. <strong>Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300.</strong> Molec. Cell 7: 1221-1231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11430825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11430825</a>] [<a href="https://doi.org/10.1016/s1097-2765(01)00272-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11430825">Hasan et al. (2001)</a> found that p300 formed a complex with flap endonuclease-1 (FEN1; <a href="/entry/600393">600393</a>) and acetylated FEN1 in vitro. Furthermore, FEN1 acetylation was observed in vivo and was enhanced upon ultraviolet treatment of human cells. Acetylation of the FEN1 C terminus by p300 significantly reduced DNA binding and nuclease activity of FEN1. PCNA was able to stimulate both acetylated and unacetylated FEN1 activity to the same extent. These results identified acetylation as a novel regulatory modification of FEN1 and suggested that p300 is not only a component of the chromatin remodeling machinery but might also play a critical role in regulating DNA metabolic events. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11430825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>TDG (<a href="/entry/601423">601423</a>) initiates repair of G/T and G/U mismatches, commonly associated with CpG islands, by removing thymine and uracil moieties. <a href="#33" class="mim-tip-reference" title="Tini, M., Benecke, A., Um, S.-J., Torchia, J., Evans, R. M., Chambon, P. <strong>Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription.</strong> Molec. Cell 9: 265-277, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11864601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11864601</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00453-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11864601">Tini et al. (2002)</a> reported that TDG associates with transcriptional coactivators CBP (<a href="/entry/600140">600140</a>) and p300 and that the resulting complexes are competent for both the excision step of repair and histone acetylation. TDG stimulated CBP transcriptional activity in transfected cells and reciprocally served as a substrate for CBP/p300 acetylation. This acetylation triggered release of CBP from DNA ternary complexes and also regulated recruitment of repair endonuclease APE (<a href="/entry/107748">107748</a>). These observations revealed a potential regulatory role for protein acetylation in base mismatch repair and a role for CBP/p300 in maintaining genomic stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11864601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Etchegaray, J.-P., Lee, C., Wade, P. A., Reppert, S. M. <strong>Rhythmic histone acetylation underlies transcription in the mammalian circadian clock.</strong> Nature 421: 177-182, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483227</a>] [<a href="https://doi.org/10.1038/nature01314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483227">Etchegaray et al. (2003)</a> demonstrated that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone (see <a href="/entry/602810">602810</a>) acetylation, and that H3 acetylation is a potential target of the inhibitory action of Cry. The promoter regions of the Per1 (<a href="/entry/602260">602260</a>), Per2 (<a href="/entry/603426">603426</a>), and Cry1 (<a href="/entry/601933">601933</a>) genes exhibited circadian rhythms in H3 acetylation and RNA polymerase II (see <a href="/entry/180660">180660</a>) binding that were synchronous with the corresponding steady-state mRNA rhythms. The histone acetyltransferase p300 precipitated with Clock (<a href="/entry/601851">601851</a>) in vivo in a time-dependent manner. Moreover, the Cry proteins inhibited a p300-induced increase in Clock/Bmal1 (<a href="/entry/602550">602550</a>)-mediated transcription. <a href="#8" class="mim-tip-reference" title="Etchegaray, J.-P., Lee, C., Wade, P. A., Reppert, S. M. <strong>Rhythmic histone acetylation underlies transcription in the mammalian circadian clock.</strong> Nature 421: 177-182, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483227</a>] [<a href="https://doi.org/10.1038/nature01314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483227">Etchegaray et al. (2003)</a> concluded that the delayed timing of the Cry1 mRNA rhythm, relative to the Per rhythms, was due to the coordinated activities of Rev-Erb-alpha (<a href="/entry/602408">602408</a>) and Clock/Bmal1, and defined a novel mechanism for circadian phase control. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Rapid turnover of the tumor suppressor protein p53 (<a href="/entry/191170">191170</a>) requires the MDM2 (<a href="/entry/164785">164785</a>) ubiquitin ligase, and both interact with p300-CBP transcriptional coactivators. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. <a href="#13" class="mim-tip-reference" title="Grossman, S. R., Deato, M. E., Brignone, C., Chan, H. M., Kung, A. L., Tagami, H., Nakatani, Y., Livingston, D. M. <strong>Polyubiquitination of p53 by a ubiquitin ligase activity of p300.</strong> Science 300: 342-344, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12690203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12690203</a>] [<a href="https://doi.org/10.1126/science.1080386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12690203">Grossman et al. (2003)</a> observed that purified p300 exhibited intrinsic ubiquitin ligase activity but was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, <a href="#13" class="mim-tip-reference" title="Grossman, S. R., Deato, M. E., Brignone, C., Chan, H. M., Kung, A. L., Tagami, H., Nakatani, Y., Livingston, D. M. <strong>Polyubiquitination of p53 by a ubiquitin ligase activity of p300.</strong> Science 300: 342-344, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12690203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12690203</a>] [<a href="https://doi.org/10.1126/science.1080386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12690203">Grossman et al. (2003)</a> concluded that generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12690203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Tsuda, M., Takahashi, S., Takahashi, Y., Asahara, H. <strong>Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9.</strong> J. Biol. Chem. 278: 27224-27229, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12732631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12732631</a>] [<a href="https://doi.org/10.1074/jbc.M303471200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12732631">Tsuda et al. (2003)</a> found that SOX9 (<a href="/entry/608160">608160</a>) used CBP and p300 as transcriptional coactivators. SOX9 bound CBP and p300 in vitro and in vivo, and both coactivators enhanced SOX9-dependent COL2A1 (<a href="/entry/120140">120140</a>) promoter activity. Disruption of the CBP-SOX9 complex inhibited COL2A1 mRNA expression and differentiation of human mesenchymal stem cells into chondrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12732631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using systems reconstituted with recombinant chromatin templates and coactivators, <a href="#1" class="mim-tip-reference" title="An, W., Kim, J., Roeder, R. G. <strong>Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.</strong> Cell 117: 735-748, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15186775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15186775</a>] [<a href="https://doi.org/10.1016/j.cell.2004.05.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15186775">An et al. (2004)</a> demonstrated the involvement of PRMT1 (<a href="/entry/602950">602950</a>) and CARM1 (<a href="/entry/603934">603934</a>) in p53 function; both independent and ordered cooperative functions of p300, PRMT1, and CARM1; and mechanisms involving direct interactions with p53 and obligatory modifications of corresponding histone substrates. Chromatin immunoprecipitation analyses confirmed the ordered accumulation of these (and other) coactivators and cognate histone modifications on a p53-responsive gene, GADD45 (<a href="/entry/126335">126335</a>), following ectopic p53 expression and/or ultraviolet irradiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15186775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Turnell, A. S., Stewart, G. S., Grand, R. J. A., Rookes, S. M., Martin, A., Yamano, H., Elledge, S. J., Gallimore, P. H. <strong>The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.</strong> Nature 438: 690-695, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16319895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16319895</a>] [<a href="https://doi.org/10.1038/nature04151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16319895">Turnell et al. (2005)</a> showed that 2 anaphase-promoting complex/cyclosome (APC/C) components, APC5 (<a href="/entry/606948">606948</a>) and APC7 (<a href="/entry/606949">606949</a>), interact directly with the coactivators CBP and p300 through protein-protein interaction domains that are evolutionarily conserved in adenovirus E1A. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. <a href="#35" class="mim-tip-reference" title="Turnell, A. S., Stewart, G. S., Grand, R. J. A., Rookes, S. M., Martin, A., Yamano, H., Elledge, S. J., Gallimore, P. H. <strong>The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.</strong> Nature 438: 690-695, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16319895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16319895</a>] [<a href="https://doi.org/10.1038/nature04151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16319895">Turnell et al. (2005)</a> also showed that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, <a href="#35" class="mim-tip-reference" title="Turnell, A. S., Stewart, G. S., Grand, R. J. A., Rookes, S. M., Martin, A., Yamano, H., Elledge, S. J., Gallimore, P. H. <strong>The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.</strong> Nature 438: 690-695, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16319895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16319895</a>] [<a href="https://doi.org/10.1038/nature04151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16319895">Turnell et al. (2005)</a> established that CBP is required for APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, <a href="#35" class="mim-tip-reference" title="Turnell, A. S., Stewart, G. S., Grand, R. J. A., Rookes, S. M., Martin, A., Yamano, H., Elledge, S. J., Gallimore, P. H. <strong>The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression.</strong> Nature 438: 690-695, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16319895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16319895</a>] [<a href="https://doi.org/10.1038/nature04151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16319895">Turnell et al. (2005)</a> concluded that their results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16319895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In vivo transcription by RNA polymerase II takes place in the context of chromatin. <a href="#14" class="mim-tip-reference" title="Guermah, M., Palhan, V. B., Tackett, A. J., Chait, B. T., Roeder, R. G. <strong>Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates.</strong> Cell 125: 275-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16630816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16630816</a>] [<a href="https://doi.org/10.1016/j.cell.2006.01.055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16630816">Guermah et al. (2006)</a> found that a purified, reconstituted RNA polymerase II system that sufficed for activator-dependent transcription on DNA templates was incapable of transcribing chromatin templates, even in the presence of factors that effected transcription in less-purified assay systems. Using a complementation and HeLa cell nuclear extract fractionation scheme, <a href="#14" class="mim-tip-reference" title="Guermah, M., Palhan, V. B., Tackett, A. J., Chait, B. T., Roeder, R. G. <strong>Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates.</strong> Cell 125: 275-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16630816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16630816</a>] [<a href="https://doi.org/10.1016/j.cell.2006.01.055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16630816">Guermah et al. (2006)</a> identified and purified an activity, designated CTEA (chromatin transcription-enabling activity), that allowed for transcription through chromatin templates in a manner that was both activator and p300/acetyl-CoA dependent. CTEA acted primarily at the elongation step and enabled RNA polymerase II machinery to transcribe efficiently through several contiguously positioned nucleosomes. <a href="#14" class="mim-tip-reference" title="Guermah, M., Palhan, V. B., Tackett, A. J., Chait, B. T., Roeder, R. G. <strong>Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates.</strong> Cell 125: 275-286, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16630816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16630816</a>] [<a href="https://doi.org/10.1016/j.cell.2006.01.055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16630816">Guermah et al. (2006)</a> identified the major functional component of CTEA as transcription elongation factor SII (TCEA1; <a href="/entry/601425">601425</a>). SII was essential for productive transcription elongation, and its function at this step was dependent on p300-dependent acetylation. These synergistic transcriptional elongation activities were potentiated by HMGB2 (<a href="/entry/163906">163906</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16630816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Liu, Y., Dentin, R., Chen, D., Hedrick, S., Ravnskjaer, K., Schenk, S., Milne, J., Meyers, D. J., Cole, P., Yates, J., III, Olefsky, J., Guarente, L., Montminy, M. <strong>A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange.</strong> Nature 456: 269-273, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18849969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18849969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18849969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18849969">Liu et al. (2008)</a> demonstrated that a fasting-inducible switch, consisting of the histone acetyltransferase p300 and the nutrient-sensing deacetylase sirtuin-1 (SIRT1; <a href="/entry/604479">604479</a>), maintains energy balance in mice through the sequential induction of CRTC2 (<a href="/entry/608972">608972</a>) and FOXO1 (<a href="/entry/136533">136533</a>). After glucagon induction, CRTC2 stimulated gluconeogenic gene expression by an association with p300, which <a href="#24" class="mim-tip-reference" title="Liu, Y., Dentin, R., Chen, D., Hedrick, S., Ravnskjaer, K., Schenk, S., Milne, J., Meyers, D. J., Cole, P., Yates, J., III, Olefsky, J., Guarente, L., Montminy, M. <strong>A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange.</strong> Nature 456: 269-273, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18849969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18849969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18849969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18849969">Liu et al. (2008)</a> showed is also activated by dephosphorylation at serine-89 during fasting. In turn, p300 increased hepatic CRTC2 activity by acetylating it at lysine-628, a site that also targets CRTC2 for degradation after its ubiquitination by the E3 ligase constitutive photomorphogenic protein (COP1; <a href="/entry/608067">608067</a>). Glucagon effects were attenuated during late fasting, when CRTC2 was downregulated owing to SIRT1-mediated deacetylation and when FOXO1 supported expression of the gluconeogenic program. Disrupting SIRT1 activity, by liver-specific knockout of the SIRT1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them. In view of the reciprocal activation of FOXO1 and its coactivator Ppar-gamma coactivator 1-alpha (PGC1-alpha; <a href="/entry/604517">604517</a>) by SIRT1 activators, <a href="#24" class="mim-tip-reference" title="Liu, Y., Dentin, R., Chen, D., Hedrick, S., Ravnskjaer, K., Schenk, S., Milne, J., Meyers, D. J., Cole, P., Yates, J., III, Olefsky, J., Guarente, L., Montminy, M. <strong>A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange.</strong> Nature 456: 269-273, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18849969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18849969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18849969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18849969">Liu et al. (2008)</a> concluded that their results illustrate how the exchange of 2 gluconeogenic regulators during fasting maintains energy balance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18849969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., Afzal, V., Ren, B., Rubin, E. M., Pennacchio, L. A. <strong>ChIP-seq accurately predicts tissue-specific activity of enhancers.</strong> Nature 457: 854-858, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19212405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19212405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19212405[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19212405">Visel et al. (2009)</a> presented the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and mapped several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. They tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. <a href="#37" class="mim-tip-reference" title="Visel, A., Blow, M. J., Li, Z., Zhang, T., Akiyama, J. A., Holt, A., Plajzer-Frick, I., Shoukry, M., Wright, C., Chen, F., Afzal, V., Ren, B., Rubin, E. M., Pennacchio, L. A. <strong>ChIP-seq accurately predicts tissue-specific activity of enhancers.</strong> Nature 457: 854-858, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19212405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19212405</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19212405[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19212405">Visel et al. (2009)</a> concluded that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggested that such datasets will be useful in the study of the role of tissue-specific enhancers in human biology and disease on a genomewide scale. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19212405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Das, C., Lucia, M. S., Hansen, K. C., Tyler, J. K. <strong>CBP/p300-mediated acetylation of histone H3 on lysine56.</strong> Nature 459: 113-117, 2009. Note: Erratum: Nature 460: 1164 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270680</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270680[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270680">Das et al. (2009)</a> demonstrated that the histone acetyltransferase CBP (<a href="/entry/600140">600140</a>) in flies, and CBP and p300 in humans, acetylate histone H3 (see <a href="/entry/601128">601128</a>) on lys56 (H3K56), whereas Drosophila sir2 and human SIRT1 and SIRT2 (<a href="/entry/604480">604480</a>) deacetylate H3K56 acetylation. The histone chaperones ASF1A (<a href="/entry/609189">609189</a>) in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF1 (see <a href="/entry/601245">601245</a>) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. <a href="#6" class="mim-tip-reference" title="Das, C., Lucia, M. S., Hansen, K. C., Tyler, J. K. <strong>CBP/p300-mediated acetylation of histone H3 on lysine56.</strong> Nature 459: 113-117, 2009. Note: Erratum: Nature 460: 1164 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270680</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270680[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270680">Das et al. (2009)</a> showed that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumors. <a href="#6" class="mim-tip-reference" title="Das, C., Lucia, M. S., Hansen, K. C., Tyler, J. K. <strong>CBP/p300-mediated acetylation of histone H3 on lysine56.</strong> Nature 459: 113-117, 2009. Note: Erratum: Nature 460: 1164 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270680</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270680[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270680">Das et al. (2009)</a> concluded that their identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation, and cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19270680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Vilhais-Neto, G. C., Maruhashi, M., Smith, K. T., Vasseur-Cognet, M., Peterson, A. S., Workman, J. L., Pourquie, O. <strong>Rere controls retinoic acid signalling and somite bilateral symmetry.</strong> Nature 463: 953-957, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20164929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20164929</a>] [<a href="https://doi.org/10.1038/nature08763" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20164929">Vilhais-Neto et al. (2010)</a> found that RERE (<a href="/entry/605226">605226</a>) forms a complex with NR2F2 (<a href="/entry/107773">107773</a>), p300, and a retinoic acid receptor, which is recruited to the retinoic acid regulatory element of retinoic acid targets, such as the RARB (<a href="/entry/180220">180220</a>) promoter. Furthermore, the knockdown of NR2F2 and/or RERE decreases retinoic acid signaling, suggesting that this complex is required to promote transcriptional activation of retinoic acid targets. The symmetrical expression of NR2F2 in the presomitic mesoderm overlaps with the symmetry of the retinoic acid signaling response, supporting its implication in the control of somitic symmetry. <a href="#36" class="mim-tip-reference" title="Vilhais-Neto, G. C., Maruhashi, M., Smith, K. T., Vasseur-Cognet, M., Peterson, A. S., Workman, J. L., Pourquie, O. <strong>Rere controls retinoic acid signalling and somite bilateral symmetry.</strong> Nature 463: 953-957, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20164929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20164929</a>] [<a href="https://doi.org/10.1038/nature08763" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20164929">Vilhais-Neto et al. (2010)</a> suggested that misregulation of this mechanism could be involved in symmetry defects of the human spine, such as those observed in patients with scoliosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20164929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S. <strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong> Science 332: 963-966, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21596989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1202845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596989">Xu et al. (2011)</a> isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices, and found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein (BMP; see <a href="/entry/600799">600799</a>) signaling, and the histone methyltransferase Ezh2 (<a href="/entry/601573">601573</a>) have modulatory roles in the fate choice. <a href="#41" class="mim-tip-reference" title="Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S. <strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong> Science 332: 963-966, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21596989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21596989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21596989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1202845" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21596989">Xu et al. (2011)</a> concluded that their studies revealed a functional 'prepattern' of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21596989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Wang, L., Gural, A., Sun, X.-J., Zhao, X., Perna, F., Huang, G., Hatlen, M. A., Vu, L., Liu, F., Xu, H., Asai, T., Xu, H., and 9 others. <strong>The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation.</strong> Science 333: 765-769, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21764752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21764752</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21764752[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1201662" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21764752">Wang et al. (2011)</a> found that AML1-ETO (see <a href="/entry/151385">151385</a>), a fusion protein generated by the t(8;21) translocation found in acute myelogenous leukemia, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal-promoting effects in human cord blood CD34+ (<a href="/entry/142230">142230</a>) cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. <a href="#38" class="mim-tip-reference" title="Wang, L., Gural, A., Sun, X.-J., Zhao, X., Perna, F., Huang, G., Hatlen, M. A., Vu, L., Liu, F., Xu, H., Asai, T., Xu, H., and 9 others. <strong>The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation.</strong> Science 333: 765-769, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21764752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21764752</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21764752[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1201662" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21764752">Wang et al. (2011)</a> concluded that lysine acetyltransferases represent a potential therapeutic target in AML. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21764752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To identify distant-acting enhancers active during craniofacial development, <a href="#4" class="mim-tip-reference" title="Attanasio, C., Nord, A. S., Zhu, Y., Blow, M. J., Li, Z., Liberton, D. K., Morrison, H., Plajzer-Frick, I., Holt, A., Hosseini, R., Phouanenavong, S., Akiyama, J. A., Shoukry, M., Afzal, V., Rubin, E. M., FitzPatrick, D. R., Ren, B., Hallgrimsson, B., Pennacchio, L. A., Visel, A. <strong>Fine tuning of craniofacial morphology by distant-acting enhancers.</strong> Science 342: 1241006, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24159046">Attanasio et al. (2013)</a> used chromatin immunoprecipitation on embryonic mouse face tissue followed by sequencing to identify noncoding genome regions bound by the enhancer-associated p300 protein. They identified more than 4,000 candidate enhancers, the majority of which were at least partially conserved between humans and mice. <a href="#4" class="mim-tip-reference" title="Attanasio, C., Nord, A. S., Zhu, Y., Blow, M. J., Li, Z., Liberton, D. K., Morrison, H., Plajzer-Frick, I., Holt, A., Hosseini, R., Phouanenavong, S., Akiyama, J. A., Shoukry, M., Afzal, V., Rubin, E. M., FitzPatrick, D. R., Ren, B., Hallgrimsson, B., Pennacchio, L. A., Visel, A. <strong>Fine tuning of craniofacial morphology by distant-acting enhancers.</strong> Science 342: 1241006, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24159046">Attanasio et al. (2013)</a> subsequently used LacZ reporter assays in transgenic mice and optical projection tomography to determine 3-dimensional expression patterns of a subset of these candidate enhancers. Further characterization of more than 200 candidate enhancer sequences in transgenic mice revealed a remarkable spatial complexity of in vivo expression patterns. Candidate enhancers were identified within the gene desert associated with cleft palate and facial morphology on chromosome 8q24, and at the ABCA4 (<a href="/entry/601691">601691</a>) locus. Targeted deletions of 3 craniofacial enhancers near genes with roles in craniofacial development (Snai2, <a href="/entry/602150">602150</a>; Msx1, <a href="/entry/142983">142983</a>; and Isl1, <a href="/entry/600366">600366</a>) resulted in changes of expression of those genes as well as quantitatively subtle yet definable alterations of craniofacial shape. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24159046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Gao, Z., Lee, P., Stafford, J. M., von Schimmelmann, M., Schaefer, A., Reinberg, D. <strong>An AUTS2-Polycomb complex activates gene expression in the CNS.</strong> Nature 516: 349-354, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25519132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25519132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25519132[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25519132">Gao et al. (2014)</a> investigated the role of AUTS2 (<a href="/entry/607270">607270</a>) as part of a previously identified Polycomb repressive complex (PRC1-AUTS2) and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrated that the casein kinase-2 (CK2; see <a href="/entry/115440">115440</a>) component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of p300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. <a href="#11" class="mim-tip-reference" title="Gao, Z., Lee, P., Stafford, J. M., von Schimmelmann, M., Schaefer, A., Reinberg, D. <strong>An AUTS2-Polycomb complex activates gene expression in the CNS.</strong> Nature 516: 349-354, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25519132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25519132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25519132[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25519132">Gao et al. (2014)</a> concluded that their findings revealed a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25519132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Ortega, E., Rengachari, S., Ibrahim, Z., Hoghoughi, N., Gaucher, J., Holehouse, A. S., Khochbin, S., Panne, D. <strong>Transcription factor dimerization activates the p300 acetyltransferase.</strong> Nature 562: 538-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-018-0621-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30323286">Ortega et al. (2018)</a> showed that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using 2 model transcription factors, IRF3 (<a href="/entry/603734">603734</a>) and STAT1 (<a href="/entry/600555">600555</a>), <a href="#29" class="mim-tip-reference" title="Ortega, E., Rengachari, S., Ibrahim, Z., Hoghoughi, N., Gaucher, J., Holehouse, A. S., Khochbin, S., Panne, D. <strong>Transcription factor dimerization activates the p300 acetyltransferase.</strong> Nature 562: 538-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30323286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30323286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30323286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-018-0621-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30323286">Ortega et al. (2018)</a> demonstrated that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30323286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By fluorescence in situ hybridization, <a href="#7" class="mim-tip-reference" title="Eckner, R., Ewen, M. E., Newsome, D., Gerdes, M., DeCaprio, J. A., Lawrence, J. B., Livingston, D. M. <strong>Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.</strong> Genes Dev. 8: 869-884, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7523245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7523245</a>] [<a href="https://doi.org/10.1101/gad.8.8.869" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7523245">Eckner et al. (1994)</a> mapped the p300 gene, symbolized EP300, to chromosome 22q13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7523245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Rubinstein-Taybi Syndrome 2</em></strong></p><p>
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In 3 unrelated patients with Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#31" class="mim-tip-reference" title="Roelfsema, J. H., White, S. J., Ariyurek, Y., Bartholdi, D., Niedrist, D., Papadia, F., Bacino, C. A., den Dunnen, J. T., van Ommen, G.-J. B., Breuning, M. H., Hennekam, R. C., Peters, D. J. M. <strong>Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.</strong> Am. J. Hum. Genet. 76: 572-580, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15706485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15706485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15706485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/429130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15706485">Roelfsema et al. (2005)</a> identified 3 different heterozygous de novo mutations in the EP300 gene (<a href="#0003">602700.0003</a>-<a href="#0005">602700.0005</a>). CREBBP and EP300 function as transcriptional coactivators in the regulation of gene expression through various signal transduction pathways. Inactivation of CREBBP also results in Rubinstein-Taybi syndrome-1 (RSTS1; <a href="/entry/180849">180849</a>), indicating that a certain level of the protein is essential for normal development. There is a direct link between loss of acetyltransferase activity and RSTS, which indicates the disorder is caused by aberrant chromatin regulation. <a href="#31" class="mim-tip-reference" title="Roelfsema, J. H., White, S. J., Ariyurek, Y., Bartholdi, D., Niedrist, D., Papadia, F., Bacino, C. A., den Dunnen, J. T., van Ommen, G.-J. B., Breuning, M. H., Hennekam, R. C., Peters, D. J. M. <strong>Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.</strong> Am. J. Hum. Genet. 76: 572-580, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15706485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15706485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15706485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/429130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15706485">Roelfsema et al. (2005)</a> stated that these were the first mutations identified in EP300 underlying a congenital disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15706485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 1 (2.6%) of 38 patients with RSTS who did not have mutations in the CREBBP gene, <a href="#43" class="mim-tip-reference" title="Zimmermann, N., Acosta, A. M. B. F., Kohlhase, J., Bartsch, O. <strong>Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.</strong> Europ. J. Hum. Genet. 15: 837-842, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299436</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201791" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17299436">Zimmermann et al. (2007)</a> identified a mutation in the EP300 gene (<a href="#0006">602700.0006</a>) predicted to result in mild protein truncation. The patient had a very mild form of the disorder. <a href="#43" class="mim-tip-reference" title="Zimmermann, N., Acosta, A. M. B. F., Kohlhase, J., Bartsch, O. <strong>Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.</strong> Europ. J. Hum. Genet. 15: 837-842, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299436</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201791" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17299436">Zimmermann et al. (2007)</a> concluded that mutations in the EP300 gene play only a minor role in the etiology of RSTS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17299436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 7-year-old boy with suspected Rubinstein-Taybi syndrome in whom sequencing and MLPA analysis of the CREBBP gene was normal, <a href="#10" class="mim-tip-reference" title="Foley, P., Bunyan, D., Stratton, J., Dillon, M., Lynch, S. A. <strong>Further case of Rubinstein-Taybi syndrome due to a deletion in EP300.</strong> Am. J. Med. Genet. 149A: 997-1000, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19353645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19353645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19353645">Foley et al. (2009)</a> identified a de novo deletion involving exons 3 to 8 in the EP300 gene (<a href="#0007">602700.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19353645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> reported heterozygous de novo mutations at highly conserved residues in the EP300 gene in 9 unrelated patients from the UK or Ireland with RSTS2. Six mutations were truncating mutations and 3 were missense (see, e.g., <a href="#0010">602700.0010</a> and <a href="#0011">602700.0011</a>) mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27465822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Menke-Hennekam Syndrome 2</em></strong></p><p>
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In 2 patients with MKHK2, 1 of whom had been studied by <a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a>, <a href="#25" class="mim-tip-reference" title="Menke, L. A., DDD Study, Gardeitchik, T., Hammond, P., Heimdal, K. R., Houge, G., Hufnagel, S. B., Ji, J., Johansson, S., Kant, S. G., Kinning, E., Leon, E. L., and 14 others. <strong>Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 176: 862-876, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29460469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29460469</a>] [<a href="https://doi.org/10.1002/ajmg.a.38626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29460469">Menke et al. (2018)</a> identified 2 heterozygous de novo mutations in EP300 (<a href="#0012">602700.0012</a>, <a href="#0013">602700.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27465822+29460469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Somatic Mutations</em></strong></p><p>
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A role for EP300 in cancer had been implied by the fact that it is targeted by viral oncoproteins (<a href="#2" class="mim-tip-reference" title="Arany, Z., Newsome, D., Oldread, E., Livingston, D. M., Eckner, R. <strong>A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.</strong> Nature 374: 81-84, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7870178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7870178</a>] [<a href="https://doi.org/10.1038/374081a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7870178">Arany et al., 1995</a>), it is fused to MLL (<a href="/entry/159555">159555</a>) in leukemia (<a href="#18" class="mim-tip-reference" title="Ida, K., Kitabayashi, I., Taki, T., Taniwaki, M., Noro, K., Yamamoto, M., Ohki, M., Hayashi, Y. <strong>Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13).</strong> Blood 90: 4699-4704, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9389684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9389684</a>]" pmid="9389684">Ida et al., 1997</a>), and 2 missense sequence alterations in EP300 were identified in epithelial malignancies (<a href="#26" class="mim-tip-reference" title="Muraoka, M., Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., Shitara, N., Chong, J.-M., Iwama, T., Miyaki, M. <strong>p300 gene alterations in colorectal and gastric carcinomas.</strong> Oncogene 12: 1565-1569, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8622873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8622873</a>]" pmid="8622873">Muraoka et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7870178+8622873+9389684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gayther, S. A., Batley, S. J., Linger, L., Bannister, A., Thorpe, K., Chin, S.-F., Daigo, Y., Russell, P., Wilson, A., Sowter, H. M., Delhanty, J. D. A., Ponder, B. A. J., Kouzarides, T., Caldas, C. <strong>Mutations truncating the EP300 acetylase in human cancers.</strong> Nature Genet. 24: 300-303, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700188</a>] [<a href="https://doi.org/10.1038/73536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700188">Gayther et al. (2000)</a> described somatic EP300 mutations (see, e.g., <a href="#0001">602700.0001</a>; <a href="#0002">602700.0002</a>) that predicted a truncated protein in 6 (3%) of 193 epithelial cancers analyzed. Of these 6 mutations, 2 were in primary tumors (a colorectal cancer and a breast cancer) and 4 were in cancer cell lines (colorectal, breast, and pancreatic). In addition, they identified a somatic in-frame insertion in a primary breast cancer and missense alterations in a primary colorectal cancer and 2 cell lines (breast and pancreatic). Inactivation of the second allele was demonstrated in 5 of the 6 cases with truncating mutations and in 2 other cases. The data showed that EP300 is mutated in epithelial cancers and provided the first evidence that it behaves as a classic tumor suppressor gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Pasqualucci, L., Dominguez-Sola, D., Chiarenza, A., Fabbri, G., Grunn, A., Trifonov, V., Kasper, L. H., Lerach, S., Tang, H., Ma, J., Rossi, D., Chadburn, A., Murty, V. V., Mullighan, C. G., Gaidano, G., Rabadan, R., Brindle, P. K., Dalla-Favera, R. <strong>Inactivating mutations of acetyltransferase genes in B-cell lymphoma.</strong> Nature 471: 189-195, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21390126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21390126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21390126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21390126">Pasqualucci et al. (2011)</a> reported that the 2 most common types of B cell non-Hodgkin lymphoma (<a href="/entry/605027">605027</a>), follicular lymphoma and diffuse large B-cell lymphoma, harbor frequent structural alterations inactivating CREBBP and, more rarely, EP300, 2 highly related histone and nonhistone acetyltransferases (HATs) that act as transcriptional coactivators in multiple signaling pathways. Overall, about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma cases display genomic deletions and/or somatic mutations that remove or inactivate the HAT coding domain of these 2 genes. These lesions usually affect 1 allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. <a href="#30" class="mim-tip-reference" title="Pasqualucci, L., Dominguez-Sola, D., Chiarenza, A., Fabbri, G., Grunn, A., Trifonov, V., Kasper, L. H., Lerach, S., Tang, H., Ma, J., Rossi, D., Chadburn, A., Murty, V. V., Mullighan, C. G., Gaidano, G., Rabadan, R., Brindle, P. K., Dalla-Favera, R. <strong>Inactivating mutations of acetyltransferase genes in B-cell lymphoma.</strong> Nature 471: 189-195, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21390126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21390126</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21390126[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21390126">Pasqualucci et al. (2011)</a> demonstrated specific defects in acetylation-mediated inactivation of the BCL6 oncoprotein (<a href="/entry/109565">109565</a>) and activation of the p53 tumor suppressor (<a href="/entry/191170">191170</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21390126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W. <strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong> Nature Genet. 44: 1310-1315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23104009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23104009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23104009[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23104009">Le Gallo et al. (2012)</a> used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors (see <a href="/entry/608089">608089</a>), and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. <a href="#20" class="mim-tip-reference" title="Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter, P., Mullikan, J. C., Merino, M. J., Bell, D. W. <strong>Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.</strong> Nature Genet. 44: 1310-1315, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23104009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23104009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23104009[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23104009">Le Gallo et al. (2012)</a> identified a high frequency of somatic mutation (8%) in the EP300 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23104009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a mother and daughter (family RF19) with autosomal dominant spinocerebellar ataxia (see, e.g., SCA1; <a href="/entry/164400">164400</a>), <a href="#28" class="mim-tip-reference" title="Nibbeling, E. A. R., Duarri, A., Verschuuren-Bemelmans, C. C., Fokkens, M. R., Karjalainen, J. M., Smeets, C. J. L. M., de Boer-Bergsma, J. J., van der Vries, G., Dooijes, D., Bampi, G. B., van Diemen, C., Brunt, E., and 9 others. <strong>Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.</strong> Brain 140: 2860-2878, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29053796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29053796</a>] [<a href="https://doi.org/10.1093/brain/awx251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29053796">Nibbeling et al. (2017)</a> identified a heterozygous 1-bp insertion (c.6693_6694insC) in the EP300 gene, predicted to result in a frameshift and premature termination (Gln2232fs70Ter) leading to a loss of the C-terminal part of the second transactivation domain. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family was 1 of 20 unrelated families with autosomal dominant SCA who underwent whole-exome sequencing. A second heterozygous missense variant (c.6020A-G, gln2007 to arg, Q2007R) at a highly conserved residue in the linker preceding the second transactivation domain was subsequently identified in a man (case DNA008784) with apparently sporadic SCA. (The Q2007R mutation also appeared as Gln2232Arg in Table 1 of the report.) This patient was 1 of 96 individuals with SCA who were screened with a gene panel. Both variants were absent from the 1000 Genomes Project database. The truncating variant was not found in the ExAC database, whereas Q2007R was found at a very low frequency in the ExAC database (8.245 x 10(-6)). Functional studies of the variants and studies of patient cells were not performed. The mother and daughter had slowly progressive gait ataxia with an unclear age at onset. Brain imaging showed loss of parenchyma in the cerebellar vermis. The unrelated patient with sporadic disease had onset of slowly progressive cerebellar ataxia at age 20 years, cerebellar atrophy on brain imaging, and spasticity. Gene network analysis suggested that EP300 is linked with known SCA genes based on predicted functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29053796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transcriptional coactivator and integrator p300 and its closely related family member CREBBP mediate multiple signal-dependent transcriptional events. <a href="#42" class="mim-tip-reference" title="Yao, T. P., Oh, S. P., Fuchs, M., Zhou, N.-D., Ch'ng, L.-E., Newsome, D., Bronson, R. T., Li, E., Livingston, D. M., Eckner, R. <strong>Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.</strong> Cell 93: 361-372, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590171</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81165-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590171">Yao et al. (1998)</a> generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and CREBBP was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and CREBBP. These results provide evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Kasper, L. H., Boussouar, F., Ney, P. A., Jackson, C. W., Rehg, J., van Deursen, J. M., Brindle, P. K. <strong>A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis.</strong> Nature 419: 738-743, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12384703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12384703</a>] [<a href="https://doi.org/10.1038/nature01062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12384703">Kasper et al. (2002)</a> demonstrated that the protein-binding KIX domains of CBP (<a href="/entry/600140">600140</a>) and p300 have nonredundant functions in mice. In mice homozygous for point mutations in the KIX domain of p300 designed to disrupt the binding surface for the transcription factors c-Myb (<a href="/entry/189990">189990</a>) and Creb (<a href="/entry/123810">123810</a>), multilineage defects occur in hematopoiesis, including anemia, B-cell deficiency, thymic hypoplasia, megakaryocytosis, and thrombocytosis. By contrast, age-matched mice homozygous for identical mutations in the KIX domain of CBP are essentially normal. There is a synergistic genetic interaction between mutations in c-MYB and mutations in the KIX domain of p300, which suggests that the binding of c-MYB to this domain of p300 is crucial for the development and function of megakaryocytes. Thus, <a href="#19" class="mim-tip-reference" title="Kasper, L. H., Boussouar, F., Ney, P. A., Jackson, C. W., Rehg, J., van Deursen, J. M., Brindle, P. K. <strong>A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis.</strong> Nature 419: 738-743, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12384703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12384703</a>] [<a href="https://doi.org/10.1038/nature01062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12384703">Kasper et al. (2002)</a> concluded that conserved domains in 2 highly related coactivators have contrasting roles in hematopoiesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12384703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Sandberg, M. L., Sutton, S. E., Pletcher, M. T., Wiltshire, T., Tarantino, L. M., Hogenesch, J. B., Cooke, M. P. <strong>c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation.</strong> Dev. Cell 8: 153-166, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15691758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15691758</a>] [<a href="https://doi.org/10.1016/j.devcel.2004.12.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15691758">Sandberg et al. (2005)</a> created mice with a homozygous met303-to-val (M303V) mutation in the Myb gene, which disrupted the interaction between Myb and p300. The biologic consequences of the mutation included thrombocytosis, megakaryocytosis, anemia, lymphopenia, and absence of eosinophils. Detailed analysis of hematopoiesis in mutant mice revealed distinct blocks in T-cell, B-cell, and red blood cell development, as well as a 10-fold increase in the number of hematopoietic stem cells. Cell cycle analysis showed that twice as many mutant hematopoietic stem cells were actively cycling in mutant mice compared with wildtype mice. <a href="#32" class="mim-tip-reference" title="Sandberg, M. L., Sutton, S. E., Pletcher, M. T., Wiltshire, T., Tarantino, L. M., Hogenesch, J. B., Cooke, M. P. <strong>c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation.</strong> Dev. Cell 8: 153-166, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15691758/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15691758</a>] [<a href="https://doi.org/10.1016/j.devcel.2004.12.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15691758">Sandberg et al. (2005)</a> concluded that MYB, through its interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15691758" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#22" class="mim-tip-reference" title="Lin, Y., Kiihl, S., Suhail, Y., Liu, S.-Y., Chou, Y., Kuang, Z., Lu, J., Khor, C. N., Lin, C.-L., Bader, J. S., Irizarry, R., Boeke, J. D. <strong>Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK.</strong> Nature 482: 251-255, 2012. Note: Retraction: Nature 503: 146 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22318606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22318606</a>] [<a href="https://doi.org/10.1038/nature10804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22318606">Lin et al. (2012)</a> reported that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), PRKAA1 (<a href="/entry/602739">602739</a>), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 (<a href="/entry/601241">601241</a>) and p300. Deacetylation of AMPK enhanced physical interaction with the upstream kinase LKB1 (<a href="/entry/602216">602216</a>), leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. The authors later found that the Methods section of their article was inaccurate. Because they could not reproduce all of their results, they retracted the article. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22318606" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 1 of 20 primary colorectal cancers (<a href="/entry/114500">114500</a>), <a href="#12" class="mim-tip-reference" title="Gayther, S. A., Batley, S. J., Linger, L., Bannister, A., Thorpe, K., Chin, S.-F., Daigo, Y., Russell, P., Wilson, A., Sowter, H. M., Delhanty, J. D. A., Ponder, B. A. J., Kouzarides, T., Caldas, C. <strong>Mutations truncating the EP300 acetylase in human cancers.</strong> Nature Genet. 24: 300-303, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700188</a>] [<a href="https://doi.org/10.1038/73536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700188">Gayther et al. (2000)</a> found a somatic arg580-to-ter (R580X) nonsense mutation in the EP300 gene resulting from a C-to-T transition at nucleotide 2837. This was associated with loss of heterozygosity (LOH). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937578 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937578;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28937578?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007284" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007284" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007284</a>
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<p>In a primary colorectal cancer (<a href="/entry/114500">114500</a>), <a href="#12" class="mim-tip-reference" title="Gayther, S. A., Batley, S. J., Linger, L., Bannister, A., Thorpe, K., Chin, S.-F., Daigo, Y., Russell, P., Wilson, A., Sowter, H. M., Delhanty, J. D. A., Ponder, B. A. J., Kouzarides, T., Caldas, C. <strong>Mutations truncating the EP300 acetylase in human cancers.</strong> Nature Genet. 24: 300-303, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10700188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10700188</a>] [<a href="https://doi.org/10.1038/73536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10700188">Gayther et al. (2000)</a> found a somatic 7861C-A transversion in exon 31 of the EP300 gene, resulting in a pro2221-to-gln amino acid substitution. This was associated with loss of heterozygosity of the other allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10700188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, ARG648TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853039 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853039;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007285" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007285" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007285</a>
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#31" class="mim-tip-reference" title="Roelfsema, J. H., White, S. J., Ariyurek, Y., Bartholdi, D., Niedrist, D., Papadia, F., Bacino, C. A., den Dunnen, J. T., van Ommen, G.-J. B., Breuning, M. H., Hennekam, R. C., Peters, D. J. M. <strong>Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.</strong> Am. J. Hum. Genet. 76: 572-580, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15706485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15706485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15706485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/429130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15706485">Roelfsema et al. (2005)</a> found a de novo 1942C-T transition in exon 10 of the EP300 gene, resulting in an arg648-to-ter (R648X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15706485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, 8-BP DEL, NT2877
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569108381 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569108381;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569108381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569108381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007286" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007286" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007286</a>
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#31" class="mim-tip-reference" title="Roelfsema, J. H., White, S. J., Ariyurek, Y., Bartholdi, D., Niedrist, D., Papadia, F., Bacino, C. A., den Dunnen, J. T., van Ommen, G.-J. B., Breuning, M. H., Hennekam, R. C., Peters, D. J. M. <strong>Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.</strong> Am. J. Hum. Genet. 76: 572-580, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15706485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15706485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15706485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/429130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15706485">Roelfsema et al. (2005)</a> found a de novo 8-bp deletion that removed nucleotides 2877-2884 from exon 15 of the EP300 gene. The 8-bp deletion resulted in a frameshift beginning at codon 959 and ending with a premature stop at codon 966. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15706485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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</span>
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</h4>
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EP300, EX1DEL
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007287" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007287" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007287</a>
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</span>
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<span class="mim-text-font">
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#31" class="mim-tip-reference" title="Roelfsema, J. H., White, S. J., Ariyurek, Y., Bartholdi, D., Niedrist, D., Papadia, F., Bacino, C. A., den Dunnen, J. T., van Ommen, G.-J. B., Breuning, M. H., Hennekam, R. C., Peters, D. J. M. <strong>Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.</strong> Am. J. Hum. Genet. 76: 572-580, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15706485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15706485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15706485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/429130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15706485">Roelfsema et al. (2005)</a> found a deletion of the first exon of the EP300 gene. It was considered probable that this deletion would lead to no expression from the affected allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15706485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, 1-BP DEL, 7100C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569122847 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569122847;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569122847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569122847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007288 OR RCV003441707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007288, RCV003441707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007288...</a>
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#43" class="mim-tip-reference" title="Zimmermann, N., Acosta, A. M. B. F., Kohlhase, J., Bartsch, O. <strong>Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.</strong> Europ. J. Hum. Genet. 15: 837-842, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299436</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201791" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17299436">Zimmermann et al. (2007)</a> identified a 1-bp deletion (7100delC) in exon 31 of the EP300 gene, The patient had a 'mild' form of the disorder with higher intelligence than other reported patients (IQ estimated at 75) and mild facial dysmorphism. The mutation is located close to the 3-prime end of the protein, was predicted to be a mild truncation, and does not alter the HAT domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17299436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, EX3-8DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007289" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007289" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007289</a>
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<p>In a 7-year-old boy with global developmental delay, slightly broad halluces but normal thumbs, and facial dysmorphism reminiscent of Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), especially while smiling, <a href="#10" class="mim-tip-reference" title="Foley, P., Bunyan, D., Stratton, J., Dillon, M., Lynch, S. A. <strong>Further case of Rubinstein-Taybi syndrome due to a deletion in EP300.</strong> Am. J. Med. Genet. 149A: 997-1000, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19353645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19353645</a>] [<a href="https://doi.org/10.1002/ajmg.a.32771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19353645">Foley et al. (2009)</a> identified heterozygosity for a de novo deletion of exon 4 of the EP300 gene; RNA sequencing revealed that exon 2 was spliced to exon 9, indicating deletion of exons 3 through 8. Neither parent carried the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19353645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569090642 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569090642;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569090642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569090642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023210" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023210" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023210</a>
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<p>In a 3-year-old boy with RSTS2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#5" class="mim-tip-reference" title="Bartsch, O., Labonte, J., Albrecht, B., Wieczorek, D., Lechno, S., Zechner, U., Haaf, T. <strong>Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 152A: 181-184, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20014264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20014264</a>] [<a href="https://doi.org/10.1002/ajmg.a.33153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20014264">Bartsch et al. (2010)</a> identified an apparently de novo heterozygous 1-bp deletion (638delG) in exon 2 of the EP300 gene, predicted to result in a frameshift and premature termination. The child had severe microcephaly, retrognathia, broad thumbs and great toes, and delayed psychomotor development with marked speech delay. He also had posterior helical pits but normal palpebral fissures, nose, and mouth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20014264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, 4-BP DEL, NT104
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037664;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs886037664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs886037664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000125469 OR RCV001175122 OR RCV002273956 OR RCV002477332" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000125469, RCV001175122, RCV002273956, RCV002477332" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000125469...</a>
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<p>In a 5-year-old Caucasian boy with a phenotype overlapping Cornelia de Lange syndrome (<a href="/entry/122470">122470</a>), <a href="#40" class="mim-tip-reference" title="Woods, S. A., Robinson, H. B., Kohler, L. J., Agamanolis, D., Sterbenz, G., Khalifa, M. <strong>Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.</strong> Am. J. Med. Genet. 164A: 251-258, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24352918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24352918</a>] [<a href="https://doi.org/10.1002/ajmg.a.36237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24352918">Woods et al. (2014)</a> made the molecular diagnosis of RSTS2 (RSTS2; <a href="/entry/613684">613684</a>) postmortem. Whole-exome sequencing identified a heterozygous c.104_107del mutation in exon 2 of the EP300 gene, resulting in a frameshift (Ser35fs). The mutation, which was confirmed by Sanger sequencing, was not found in either parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24352918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, PHE1595VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057517732 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057517732;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1057517732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1057517732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000414599 OR RCV000433095 OR RCV000509054 OR RCV000624116 OR RCV003401394" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000414599, RCV000433095, RCV000509054, RCV000624116, RCV003401394" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000414599...</a>
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<p><a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> reported a 5-year-old girl (patient 5) with Rubinstein-Taybi syndrome (RSTS2; <a href="/entry/613684">613684</a>) who was found by whole-exome sequencing as part of the Deciphering Developmental Disorders study (<a href="#9" class="mim-tip-reference" title="Firth, H. V., Wright, C. F., D.D.D. Study. <strong>The Deciphering Developmental Disorder study.</strong> Dev. Med. Child Neurol. 53: 702-703, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21679367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21679367</a>] [<a href="https://doi.org/10.1111/j.1469-8749.2011.04032.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21679367">Firth et al., 2011</a>) to have a de novo heterozygous c.4783T-G transversion (c.4783T-G, NM_001429.3) in the EP300 gene, resulting in a phe1595-to-val (F1595V) substitution at a highly conserved residue. <a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> confirmed the mutation by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27465822+21679367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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EP300, ASN1286SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555910821 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555910821;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1555910821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1555910821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000439427 OR RCV001260706 OR RCV002244870 OR RCV002252119 OR RCV003401414" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000439427, RCV001260706, RCV002244870, RCV002252119, RCV003401414" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000439427...</a>
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<p>By direct sequencing of the EP300 gene in a 2-year-old boy (patient 9) with typical features of Rubinstein-Taybi syndrome-2 (RSTS2; <a href="/entry/613684">613684</a>), <a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> identified a de novo heterozygous c.3857A-G transition (c.3857-A-G, NM_001429.3), resulting in an asn1286-to-ser (N1286S) substitution at a highly conserved residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27465822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 MENKE-HENNEKAM SYNDROME 2</strong>
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EP300, GLN1824PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569120903 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569120903;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569120903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569120903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000757970 OR RCV003886433" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000757970, RCV003886433" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000757970...</a>
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<p>In a 17-year-old girl from the UK (patient E1) with Menke-Hennekam syndrome-2 (MKHK2; <a href="/entry/618333">618333</a>), <a href="#25" class="mim-tip-reference" title="Menke, L. A., DDD Study, Gardeitchik, T., Hammond, P., Heimdal, K. R., Houge, G., Hufnagel, S. B., Ji, J., Johansson, S., Kant, S. G., Kinning, E., Leon, E. L., and 14 others. <strong>Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 176: 862-876, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29460469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29460469</a>] [<a href="https://doi.org/10.1002/ajmg.a.38626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29460469">Menke et al. (2018)</a> identified a heterozygous A-to-C transversion at nucleotide 5471 (c.5471A-C, NM_001429.3) in exon 31 of the EP300 gene, resulting in a glutamine-to-proline substitution at codon 1824 (Q1824P). This patient had been reported by <a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> as patient 6. <a href="#25" class="mim-tip-reference" title="Menke, L. A., DDD Study, Gardeitchik, T., Hammond, P., Heimdal, K. R., Houge, G., Hufnagel, S. B., Ji, J., Johansson, S., Kant, S. G., Kinning, E., Leon, E. L., and 14 others. <strong>Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 176: 862-876, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29460469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29460469</a>] [<a href="https://doi.org/10.1002/ajmg.a.38626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29460469">Menke et al. (2018)</a> and <a href="#15" class="mim-tip-reference" title="Hamilton, M. J., Newbury-Ecob, R., Holder-Espinasse, M., Yau, S., Lillis, S., Hurst, J. A., Clement, E., Reardon, W., Joss, S., Hobson, E., Blyth, M., Al-Shehhi, M., Lynch, S. A., DDD study, Suri, M. <strong>Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.</strong> Clin. Dysmorph. 25: 135-147, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27465822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27465822</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27465822">Hamilton et al. (2016)</a> demonstrated that this mutation occurred as a de novo event. The Q1824P mutation was not found in the ESP or gnomAD databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27465822+29460469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 MENKE-HENNEKAM SYNDROME 2</strong>
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EP300, 3-BP DEL, NT5492
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569120910 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569120910;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569120910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569120910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000757971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000757971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000757971</a>
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<p>In a 14-year-old girl from the Netherlands (patient E2) with Menke-Hennekam syndrome-2 (MKHK2; <a href="/entry/618333">618333</a>), <a href="#25" class="mim-tip-reference" title="Menke, L. A., DDD Study, Gardeitchik, T., Hammond, P., Heimdal, K. R., Houge, G., Hufnagel, S. B., Ji, J., Johansson, S., Kant, S. G., Kinning, E., Leon, E. L., and 14 others. <strong>Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 176: 862-876, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29460469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29460469</a>] [<a href="https://doi.org/10.1002/ajmg.a.38626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29460469">Menke et al. (2018)</a> identified a heterozygous 3-basepair deletion in exon 31 of the EP300 gene (c.5492_5494del, NM_001429.3) that resulted in deletion of arginine-1831 (arg1831del). <a href="#25" class="mim-tip-reference" title="Menke, L. A., DDD Study, Gardeitchik, T., Hammond, P., Heimdal, K. R., Houge, G., Hufnagel, S. B., Ji, J., Johansson, S., Kant, S. G., Kinning, E., Leon, E. L., and 14 others. <strong>Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome.</strong> Am. J. Med. Genet. 176: 862-876, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29460469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29460469</a>] [<a href="https://doi.org/10.1002/ajmg.a.38626" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29460469">Menke et al. (2018)</a> demonstrated that this mutation occurred as a de novo event. The arg1831del mutation was not found in the ESP or gnomAD databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29460469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Arany, Z., Sellers, W. R., Livingston, D. M., Eckner, R.
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[<a href="https://doi.org/10.1016/0092-8674(94)90127-9" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24159046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24159046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24159046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24159046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1241006" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20014264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20014264</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20014264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature01314" target="_blank">Full Text</a>]
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<a id="42" class="mim-anchor"></a>
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<a id="Yao1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yao, T. P., Oh, S. P., Fuchs, M., Zhou, N.-D., Ch'ng, L.-E., Newsome, D., Bronson, R. T., Li, E., Livingston, D. M., Eckner, R.
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<strong>Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.</strong>
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Cell 93: 361-372, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)81165-4" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="43" class="mim-anchor"></a>
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<a id="Zimmermann2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zimmermann, N., Acosta, A. M. B. F., Kohlhase, J., Bartsch, O.
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<strong>Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.</strong>
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Europ. J. Hum. Genet. 15: 837-842, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299436</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17299436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201791" target="_blank">Full Text</a>]
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</p>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 02/26/2019
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</span>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 02/22/2019<br>Cassandra L. Kniffin - updated : 11/15/2017<br>Michael Muriello - updated : 03/02/2017<br>Ada Hamosh - updated : 6/2/2015<br>Ada Hamosh - updated : 2/3/2014<br>Ada Hamosh - updated : 2/7/2013<br>Ada Hamosh - updated : 3/7/2012<br>Ada Hamosh - updated : 8/30/2011<br>Ada Hamosh - updated : 6/14/2011<br>Ada Hamosh - updated : 6/6/2011<br>Cassandra L. Kniffin - updated : 1/6/2011<br>Ada Hamosh - updated : 4/22/2010<br>Matthew B. Gross - updated : 3/8/2010<br>Patricia A. Hartz - updated : 12/8/2009<br>Marla J. F. O'Neill - updated : 10/30/2009<br>Ada Hamosh - updated : 9/9/2009<br>Ada Hamosh - updated : 5/19/2009<br>Ada Hamosh - updated : 3/9/2009<br>Ada Hamosh - updated : 11/26/2008<br>Ada Hamosh - updated : 3/20/2008<br>Cassandra L. Kniffin - updated : 8/13/2007<br>Ada Hamosh - updated : 1/30/2006<br>Victor A. McKusick - updated : 3/11/2005<br>Patricia A. Hartz - updated : 2/23/2005<br>Stylianos E. Antonarakis - updated : 8/5/2004<br>Ada Hamosh - updated : 4/22/2003<br>Ada Hamosh - updated : 2/21/2003<br>Ada Hamosh -updated : 11/12/2002<br>Stylianos E. Antonarakis - updated : 9/23/2002<br>Stylianos E. Antonarakis - updated : 11/5/2001<br>Stylianos E. Antonarakis - updated : 7/3/2001<br>Ada Hamosh - updated : 3/12/2001<br>Victor A. McKusick - updated : 3/1/2000<br>Patti M. Sherman - updated : 4/16/1999<br>Ada Hamosh - updated : 4/15/1999
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 6/9/1998
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/01/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 03/02/2021<br>alopez : 02/26/2019<br>alopez : 02/25/2019<br>alopez : 02/22/2019<br>alopez : 11/17/2017<br>ckniffin : 11/15/2017<br>carol : 03/03/2017<br>carol : 03/02/2017<br>carol : 02/07/2017<br>carol : 02/06/2017<br>carol : 04/27/2016<br>alopez : 6/2/2015<br>carol : 6/16/2014<br>alopez : 2/3/2014<br>alopez : 2/3/2014<br>carol : 11/7/2013<br>carol : 9/16/2013<br>mgross : 2/7/2013<br>alopez : 2/7/2013<br>alopez : 2/7/2013<br>mgross : 2/5/2013<br>alopez : 3/12/2012<br>terry : 3/7/2012<br>alopez : 9/2/2011<br>terry : 8/30/2011<br>alopez : 6/16/2011<br>terry : 6/14/2011<br>alopez : 6/13/2011<br>terry : 6/6/2011<br>wwang : 1/25/2011<br>ckniffin : 1/6/2011<br>alopez : 4/23/2010<br>terry : 4/22/2010<br>wwang : 3/10/2010<br>mgross : 3/8/2010<br>mgross : 1/4/2010<br>terry : 12/8/2009<br>carol : 11/5/2009<br>terry : 10/30/2009<br>terry : 9/9/2009<br>alopez : 6/4/2009<br>terry : 5/19/2009<br>alopez : 3/10/2009<br>terry : 3/9/2009<br>alopez : 12/10/2008<br>terry : 11/26/2008<br>alopez : 3/20/2008<br>wwang : 8/23/2007<br>ckniffin : 8/13/2007<br>ckniffin : 8/13/2007<br>ckniffin : 8/13/2007<br>alopez : 2/1/2006<br>terry : 1/30/2006<br>wwang : 3/18/2005<br>wwang : 3/14/2005<br>terry : 3/11/2005<br>mgross : 2/23/2005<br>mgross : 8/5/2004<br>alopez : 4/22/2003<br>terry : 4/22/2003<br>alopez : 2/24/2003<br>alopez : 2/24/2003<br>terry : 2/21/2003<br>alopez : 11/13/2002<br>terry : 11/12/2002<br>mgross : 9/23/2002<br>mgross : 11/5/2001<br>mgross : 7/3/2001<br>alopez : 3/14/2001<br>terry : 3/12/2001<br>mcapotos : 8/1/2000<br>alopez : 3/1/2000<br>terry : 3/1/2000<br>psherman : 4/16/1999<br>alopez : 4/15/1999<br>carol : 8/27/1998<br>carol : 6/11/1998
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602700
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<div>
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<h3>
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<span class="mim-font">
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E1A-BINDING PROTEIN, 300-KD; EP300
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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p300
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: EP300</em></strong>
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</span>
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<strong>
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<em>
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Cytogenetic location: 22q13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 22:41,092,592-41,180,077 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<td rowspan="3">
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<span class="mim-font">
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22q13.2
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<td>
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<span class="mim-font">
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Colorectal cancer, somatic
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</td>
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<td>
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<span class="mim-font">
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114500
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Menke-Hennekam syndrome 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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618333
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<td>
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<span class="mim-font">
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Autosomal dominant
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</td>
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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Rubinstein-Taybi syndrome 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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613684
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The EP300 gene encodes p300, a histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation (Gayther et al., 2000). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability to interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. Eckner et al. (1994) isolated a cDNA encoding full-length human p300. p300 contains 3 cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. p300 and CREB-binding protein (CREBBP, or CBP; 600140) are highly related in primary structure (Arany et al., 1994). Several protein motifs such as a bromodomain, a KIX domain, and 3 regions rich in cys/his residues are well conserved between these 2 proteins. </p><p>Nibbeling et al. (2017) noted that EP300 is strongly expressed in human cerebellum as well as in other brain regions. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lin et al. (2001) identified a compactly folded 46-residue domain in CBP and p300, the IRF3-binding domain (IBID), and determined its structure by nuclear magnetic resonance spectroscopy. IBID has a helical framework containing an apparently flexible polyglutamine loop that participates in ligand binding. Spectroscopic data indicated that induced folding accompanies association of IBID with its partners, which exhibit no evident sequence similarities. IBID is an important contributor to signal integration by CBP and p300. </p><p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Liu et al. (2008) described a high resolution x-ray crystal structure of a semisynthetic heterodimeric p300 HAT domain in complex with a bisubstrate inhibitor, Lys-CoA. This structure showed that p300/CBP is a distant cousin of other structurally characterized HATs, but revealed several novel features that explain the broad substrate specificity and preference for nearby basic residues. Based on this structure and accompanying biochemical data, Liu et al. (2008) proposed that p300/CBP uses an unusual hit-and-run (Theorell-Chance) catalytic mechanism that is distinct from other characterized HATs. Several disease-associated mutations could also be readily accounted for by the p300 HAT structure. </p><p>Ortega et al. (2018) described a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighboring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Ortega et al. (2018) concluded that their data explained how cellular signaling and the activation and dimerization of transcription factors control the activation of p300, and therefore explained why gene transcription is associated with chromatin acetylation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Eckner et al. (1994) examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. They showed that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements. </p><p>Weaver et al. (1998) identified EP300/CREBBP and IRF3 (603734) as components of DRAF1 (double-stranded RNA-activated factor-1), a positive regulator of interferon-stimulated gene transcription that functions as a direct response to viral infection. </p><p>The cytokines LIF (159540) and BMP2 (112261) signal through different receptors and transcription factors, namely STATs and SMADs, respectively. Nakashima et al. (1999) found that LIF and BMP2 act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacted physically with STAT3 (102582) at its amino terminus in a cytokine stimulation-independent manner, and with SMAD1 (601595) at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and SMAD1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neuronal progenitors. </p><p>Hasan et al. (2001) demonstrated that p300 may have a role in DNA repair synthesis through its interaction with proliferating cell nuclear antigen (PCNA; 176740). Hasan et al. (2001) demonstrated that in vitro and in vivo p300 forms a complex with PCNA that does not depend on the S phase of the cell cycle. A large fraction of both p300 and PCNA colocalized to speckled structures in the nucleus. Furthermore, the endogenous p300-PCNA complex stimulates DNA synthesis in vitro. Chromatin immunoprecipitation experiments indicated that p300 is associated with freshly synthesized DNA after ultraviolet irradiation. Hasan et al. (2001) suggested the p300 may participate in chromatin remodeling at DNA lesion sites to facilitate PCNA function in DNA repair synthesis. </p><p>Hasan et al. (2001) found that p300 formed a complex with flap endonuclease-1 (FEN1; 600393) and acetylated FEN1 in vitro. Furthermore, FEN1 acetylation was observed in vivo and was enhanced upon ultraviolet treatment of human cells. Acetylation of the FEN1 C terminus by p300 significantly reduced DNA binding and nuclease activity of FEN1. PCNA was able to stimulate both acetylated and unacetylated FEN1 activity to the same extent. These results identified acetylation as a novel regulatory modification of FEN1 and suggested that p300 is not only a component of the chromatin remodeling machinery but might also play a critical role in regulating DNA metabolic events. </p><p>TDG (601423) initiates repair of G/T and G/U mismatches, commonly associated with CpG islands, by removing thymine and uracil moieties. Tini et al. (2002) reported that TDG associates with transcriptional coactivators CBP (600140) and p300 and that the resulting complexes are competent for both the excision step of repair and histone acetylation. TDG stimulated CBP transcriptional activity in transfected cells and reciprocally served as a substrate for CBP/p300 acetylation. This acetylation triggered release of CBP from DNA ternary complexes and also regulated recruitment of repair endonuclease APE (107748). These observations revealed a potential regulatory role for protein acetylation in base mismatch repair and a role for CBP/p300 in maintaining genomic stability. </p><p>Etchegaray et al. (2003) demonstrated that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone (see 602810) acetylation, and that H3 acetylation is a potential target of the inhibitory action of Cry. The promoter regions of the Per1 (602260), Per2 (603426), and Cry1 (601933) genes exhibited circadian rhythms in H3 acetylation and RNA polymerase II (see 180660) binding that were synchronous with the corresponding steady-state mRNA rhythms. The histone acetyltransferase p300 precipitated with Clock (601851) in vivo in a time-dependent manner. Moreover, the Cry proteins inhibited a p300-induced increase in Clock/Bmal1 (602550)-mediated transcription. Etchegaray et al. (2003) concluded that the delayed timing of the Cry1 mRNA rhythm, relative to the Per rhythms, was due to the coordinated activities of Rev-Erb-alpha (602408) and Clock/Bmal1, and defined a novel mechanism for circadian phase control. </p><p>Rapid turnover of the tumor suppressor protein p53 (191170) requires the MDM2 (164785) ubiquitin ligase, and both interact with p300-CBP transcriptional coactivators. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Grossman et al. (2003) observed that purified p300 exhibited intrinsic ubiquitin ligase activity but was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, Grossman et al. (2003) concluded that generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300. </p><p>Tsuda et al. (2003) found that SOX9 (608160) used CBP and p300 as transcriptional coactivators. SOX9 bound CBP and p300 in vitro and in vivo, and both coactivators enhanced SOX9-dependent COL2A1 (120140) promoter activity. Disruption of the CBP-SOX9 complex inhibited COL2A1 mRNA expression and differentiation of human mesenchymal stem cells into chondrocytes. </p><p>Using systems reconstituted with recombinant chromatin templates and coactivators, An et al. (2004) demonstrated the involvement of PRMT1 (602950) and CARM1 (603934) in p53 function; both independent and ordered cooperative functions of p300, PRMT1, and CARM1; and mechanisms involving direct interactions with p53 and obligatory modifications of corresponding histone substrates. Chromatin immunoprecipitation analyses confirmed the ordered accumulation of these (and other) coactivators and cognate histone modifications on a p53-responsive gene, GADD45 (126335), following ectopic p53 expression and/or ultraviolet irradiation. </p><p>Turnell et al. (2005) showed that 2 anaphase-promoting complex/cyclosome (APC/C) components, APC5 (606948) and APC7 (606949), interact directly with the coactivators CBP and p300 through protein-protein interaction domains that are evolutionarily conserved in adenovirus E1A. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. Turnell et al. (2005) also showed that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, Turnell et al. (2005) established that CBP is required for APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, Turnell et al. (2005) concluded that their results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation. </p><p>In vivo transcription by RNA polymerase II takes place in the context of chromatin. Guermah et al. (2006) found that a purified, reconstituted RNA polymerase II system that sufficed for activator-dependent transcription on DNA templates was incapable of transcribing chromatin templates, even in the presence of factors that effected transcription in less-purified assay systems. Using a complementation and HeLa cell nuclear extract fractionation scheme, Guermah et al. (2006) identified and purified an activity, designated CTEA (chromatin transcription-enabling activity), that allowed for transcription through chromatin templates in a manner that was both activator and p300/acetyl-CoA dependent. CTEA acted primarily at the elongation step and enabled RNA polymerase II machinery to transcribe efficiently through several contiguously positioned nucleosomes. Guermah et al. (2006) identified the major functional component of CTEA as transcription elongation factor SII (TCEA1; 601425). SII was essential for productive transcription elongation, and its function at this step was dependent on p300-dependent acetylation. These synergistic transcriptional elongation activities were potentiated by HMGB2 (163906). </p><p>Liu et al. (2008) demonstrated that a fasting-inducible switch, consisting of the histone acetyltransferase p300 and the nutrient-sensing deacetylase sirtuin-1 (SIRT1; 604479), maintains energy balance in mice through the sequential induction of CRTC2 (608972) and FOXO1 (136533). After glucagon induction, CRTC2 stimulated gluconeogenic gene expression by an association with p300, which Liu et al. (2008) showed is also activated by dephosphorylation at serine-89 during fasting. In turn, p300 increased hepatic CRTC2 activity by acetylating it at lysine-628, a site that also targets CRTC2 for degradation after its ubiquitination by the E3 ligase constitutive photomorphogenic protein (COP1; 608067). Glucagon effects were attenuated during late fasting, when CRTC2 was downregulated owing to SIRT1-mediated deacetylation and when FOXO1 supported expression of the gluconeogenic program. Disrupting SIRT1 activity, by liver-specific knockout of the SIRT1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them. In view of the reciprocal activation of FOXO1 and its coactivator Ppar-gamma coactivator 1-alpha (PGC1-alpha; 604517) by SIRT1 activators, Liu et al. (2008) concluded that their results illustrate how the exchange of 2 gluconeogenic regulators during fasting maintains energy balance. </p><p>Visel et al. (2009) presented the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and mapped several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. They tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Visel et al. (2009) concluded that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggested that such datasets will be useful in the study of the role of tissue-specific enhancers in human biology and disease on a genomewide scale. </p><p>Das et al. (2009) demonstrated that the histone acetyltransferase CBP (600140) in flies, and CBP and p300 in humans, acetylate histone H3 (see 601128) on lys56 (H3K56), whereas Drosophila sir2 and human SIRT1 and SIRT2 (604480) deacetylate H3K56 acetylation. The histone chaperones ASF1A (609189) in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF1 (see 601245) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. Das et al. (2009) showed that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumors. Das et al. (2009) concluded that their identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation, and cancer. </p><p>Vilhais-Neto et al. (2010) found that RERE (605226) forms a complex with NR2F2 (107773), p300, and a retinoic acid receptor, which is recruited to the retinoic acid regulatory element of retinoic acid targets, such as the RARB (180220) promoter. Furthermore, the knockdown of NR2F2 and/or RERE decreases retinoic acid signaling, suggesting that this complex is required to promote transcriptional activation of retinoic acid targets. The symmetrical expression of NR2F2 in the presomitic mesoderm overlaps with the symmetry of the retinoic acid signaling response, supporting its implication in the control of somitic symmetry. Vilhais-Neto et al. (2010) suggested that misregulation of this mechanism could be involved in symmetry defects of the human spine, such as those observed in patients with scoliosis. </p><p>Xu et al. (2011) isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices, and found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein (BMP; see 600799) signaling, and the histone methyltransferase Ezh2 (601573) have modulatory roles in the fate choice. Xu et al. (2011) concluded that their studies revealed a functional 'prepattern' of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction. </p><p>Wang et al. (2011) found that AML1-ETO (see 151385), a fusion protein generated by the t(8;21) translocation found in acute myelogenous leukemia, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal-promoting effects in human cord blood CD34+ (142230) cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Wang et al. (2011) concluded that lysine acetyltransferases represent a potential therapeutic target in AML. </p><p>To identify distant-acting enhancers active during craniofacial development, Attanasio et al. (2013) used chromatin immunoprecipitation on embryonic mouse face tissue followed by sequencing to identify noncoding genome regions bound by the enhancer-associated p300 protein. They identified more than 4,000 candidate enhancers, the majority of which were at least partially conserved between humans and mice. Attanasio et al. (2013) subsequently used LacZ reporter assays in transgenic mice and optical projection tomography to determine 3-dimensional expression patterns of a subset of these candidate enhancers. Further characterization of more than 200 candidate enhancer sequences in transgenic mice revealed a remarkable spatial complexity of in vivo expression patterns. Candidate enhancers were identified within the gene desert associated with cleft palate and facial morphology on chromosome 8q24, and at the ABCA4 (601691) locus. Targeted deletions of 3 craniofacial enhancers near genes with roles in craniofacial development (Snai2, 602150; Msx1, 142983; and Isl1, 600366) resulted in changes of expression of those genes as well as quantitatively subtle yet definable alterations of craniofacial shape. </p><p>Gao et al. (2014) investigated the role of AUTS2 (607270) as part of a previously identified Polycomb repressive complex (PRC1-AUTS2) and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrated that the casein kinase-2 (CK2; see 115440) component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of p300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. Gao et al. (2014) concluded that their findings revealed a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. </p><p>Ortega et al. (2018) showed that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using 2 model transcription factors, IRF3 (603734) and STAT1 (600555), Ortega et al. (2018) demonstrated that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>By fluorescence in situ hybridization, Eckner et al. (1994) mapped the p300 gene, symbolized EP300, to chromosome 22q13. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Rubinstein-Taybi Syndrome 2</em></strong></p><p>
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In 3 unrelated patients with Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Roelfsema et al. (2005) identified 3 different heterozygous de novo mutations in the EP300 gene (602700.0003-602700.0005). CREBBP and EP300 function as transcriptional coactivators in the regulation of gene expression through various signal transduction pathways. Inactivation of CREBBP also results in Rubinstein-Taybi syndrome-1 (RSTS1; 180849), indicating that a certain level of the protein is essential for normal development. There is a direct link between loss of acetyltransferase activity and RSTS, which indicates the disorder is caused by aberrant chromatin regulation. Roelfsema et al. (2005) stated that these were the first mutations identified in EP300 underlying a congenital disorder. </p><p>In 1 (2.6%) of 38 patients with RSTS who did not have mutations in the CREBBP gene, Zimmermann et al. (2007) identified a mutation in the EP300 gene (602700.0006) predicted to result in mild protein truncation. The patient had a very mild form of the disorder. Zimmermann et al. (2007) concluded that mutations in the EP300 gene play only a minor role in the etiology of RSTS. </p><p>In a 7-year-old boy with suspected Rubinstein-Taybi syndrome in whom sequencing and MLPA analysis of the CREBBP gene was normal, Foley et al. (2009) identified a de novo deletion involving exons 3 to 8 in the EP300 gene (602700.0007). </p><p>Hamilton et al. (2016) reported heterozygous de novo mutations at highly conserved residues in the EP300 gene in 9 unrelated patients from the UK or Ireland with RSTS2. Six mutations were truncating mutations and 3 were missense (see, e.g., 602700.0010 and 602700.0011) mutations. </p><p><strong><em>Menke-Hennekam Syndrome 2</em></strong></p><p>
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In 2 patients with MKHK2, 1 of whom had been studied by Hamilton et al. (2016), Menke et al. (2018) identified 2 heterozygous de novo mutations in EP300 (602700.0012, 602700.0013). </p><p><strong><em>Somatic Mutations</em></strong></p><p>
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A role for EP300 in cancer had been implied by the fact that it is targeted by viral oncoproteins (Arany et al., 1995), it is fused to MLL (159555) in leukemia (Ida et al., 1997), and 2 missense sequence alterations in EP300 were identified in epithelial malignancies (Muraoka et al., 1996). </p><p>Gayther et al. (2000) described somatic EP300 mutations (see, e.g., 602700.0001; 602700.0002) that predicted a truncated protein in 6 (3%) of 193 epithelial cancers analyzed. Of these 6 mutations, 2 were in primary tumors (a colorectal cancer and a breast cancer) and 4 were in cancer cell lines (colorectal, breast, and pancreatic). In addition, they identified a somatic in-frame insertion in a primary breast cancer and missense alterations in a primary colorectal cancer and 2 cell lines (breast and pancreatic). Inactivation of the second allele was demonstrated in 5 of the 6 cases with truncating mutations and in 2 other cases. The data showed that EP300 is mutated in epithelial cancers and provided the first evidence that it behaves as a classic tumor suppressor gene. </p><p>Pasqualucci et al. (2011) reported that the 2 most common types of B cell non-Hodgkin lymphoma (605027), follicular lymphoma and diffuse large B-cell lymphoma, harbor frequent structural alterations inactivating CREBBP and, more rarely, EP300, 2 highly related histone and nonhistone acetyltransferases (HATs) that act as transcriptional coactivators in multiple signaling pathways. Overall, about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma cases display genomic deletions and/or somatic mutations that remove or inactivate the HAT coding domain of these 2 genes. These lesions usually affect 1 allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. Pasqualucci et al. (2011) demonstrated specific defects in acetylation-mediated inactivation of the BCL6 oncoprotein (109565) and activation of the p53 tumor suppressor (191170). </p><p>Le Gallo et al. (2012) used whole-exome sequencing to comprehensively search for somatic mutations in 13 primary serous endometrial tumors (see 608089), and subsequently resequenced 18 genes that were mutated in more than 1 tumor and/or were components of an enriched functional grouping from 40 additional serous tumors. Le Gallo et al. (2012) identified a high frequency of somatic mutation (8%) in the EP300 gene. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a mother and daughter (family RF19) with autosomal dominant spinocerebellar ataxia (see, e.g., SCA1; 164400), Nibbeling et al. (2017) identified a heterozygous 1-bp insertion (c.6693_6694insC) in the EP300 gene, predicted to result in a frameshift and premature termination (Gln2232fs70Ter) leading to a loss of the C-terminal part of the second transactivation domain. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The family was 1 of 20 unrelated families with autosomal dominant SCA who underwent whole-exome sequencing. A second heterozygous missense variant (c.6020A-G, gln2007 to arg, Q2007R) at a highly conserved residue in the linker preceding the second transactivation domain was subsequently identified in a man (case DNA008784) with apparently sporadic SCA. (The Q2007R mutation also appeared as Gln2232Arg in Table 1 of the report.) This patient was 1 of 96 individuals with SCA who were screened with a gene panel. Both variants were absent from the 1000 Genomes Project database. The truncating variant was not found in the ExAC database, whereas Q2007R was found at a very low frequency in the ExAC database (8.245 x 10(-6)). Functional studies of the variants and studies of patient cells were not performed. The mother and daughter had slowly progressive gait ataxia with an unclear age at onset. Brain imaging showed loss of parenchyma in the cerebellar vermis. The unrelated patient with sporadic disease had onset of slowly progressive cerebellar ataxia at age 20 years, cerebellar atrophy on brain imaging, and spasticity. Gene network analysis suggested that EP300 is linked with known SCA genes based on predicted functions. </p>
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<strong>Animal Model</strong>
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<p>The transcriptional coactivator and integrator p300 and its closely related family member CREBBP mediate multiple signal-dependent transcriptional events. Yao et al. (1998) generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and CREBBP was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and CREBBP. These results provide evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development. </p><p>Kasper et al. (2002) demonstrated that the protein-binding KIX domains of CBP (600140) and p300 have nonredundant functions in mice. In mice homozygous for point mutations in the KIX domain of p300 designed to disrupt the binding surface for the transcription factors c-Myb (189990) and Creb (123810), multilineage defects occur in hematopoiesis, including anemia, B-cell deficiency, thymic hypoplasia, megakaryocytosis, and thrombocytosis. By contrast, age-matched mice homozygous for identical mutations in the KIX domain of CBP are essentially normal. There is a synergistic genetic interaction between mutations in c-MYB and mutations in the KIX domain of p300, which suggests that the binding of c-MYB to this domain of p300 is crucial for the development and function of megakaryocytes. Thus, Kasper et al. (2002) concluded that conserved domains in 2 highly related coactivators have contrasting roles in hematopoiesis. </p><p>Sandberg et al. (2005) created mice with a homozygous met303-to-val (M303V) mutation in the Myb gene, which disrupted the interaction between Myb and p300. The biologic consequences of the mutation included thrombocytosis, megakaryocytosis, anemia, lymphopenia, and absence of eosinophils. Detailed analysis of hematopoiesis in mutant mice revealed distinct blocks in T-cell, B-cell, and red blood cell development, as well as a 10-fold increase in the number of hematopoietic stem cells. Cell cycle analysis showed that twice as many mutant hematopoietic stem cells were actively cycling in mutant mice compared with wildtype mice. Sandberg et al. (2005) concluded that MYB, through its interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells. </p>
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<strong>History</strong>
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<p>Lin et al. (2012) reported that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), PRKAA1 (602739), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 (601241) and p300. Deacetylation of AMPK enhanced physical interaction with the upstream kinase LKB1 (602216), leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. The authors later found that the Methods section of their article was inaccurate. Because they could not reproduce all of their results, they retracted the article. </p>
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<strong>ALLELIC VARIANTS</strong>
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<strong>13 Selected Examples):</strong>
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<strong>.0001 COLORECTAL CANCER, SOMATIC</strong>
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EP300, ARG580TER
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<br />
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SNP: rs137853038,
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ClinVar: RCV000007283, RCV001255736
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<p>In 1 of 20 primary colorectal cancers (114500), Gayther et al. (2000) found a somatic arg580-to-ter (R580X) nonsense mutation in the EP300 gene resulting from a C-to-T transition at nucleotide 2837. This was associated with loss of heterozygosity (LOH). </p>
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<span class="mim-font">
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<strong>.0002 COLORECTAL CANCER, SOMATIC</strong>
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EP300, PRO2221GLN
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SNP: rs28937578,
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gnomAD: rs28937578,
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ClinVar: RCV000007284
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<span class="mim-text-font">
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<p>In a primary colorectal cancer (114500), Gayther et al. (2000) found a somatic 7861C-A transversion in exon 31 of the EP300 gene, resulting in a pro2221-to-gln amino acid substitution. This was associated with loss of heterozygosity of the other allele. </p>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EP300, ARG648TER
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<br />
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SNP: rs137853039,
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ClinVar: RCV000007285
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Roelfsema et al. (2005) found a de novo 1942C-T transition in exon 10 of the EP300 gene, resulting in an arg648-to-ter (R648X) mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 RUBINSTEIN-TAYBI SYNDROME 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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EP300, 8-BP DEL, NT2877
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<br />
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SNP: rs1569108381,
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ClinVar: RCV000007286
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Roelfsema et al. (2005) found a de novo 8-bp deletion that removed nucleotides 2877-2884 from exon 15 of the EP300 gene. The 8-bp deletion resulted in a frameshift beginning at codon 959 and ending with a premature stop at codon 966. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
EP300, EX1DEL
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<br />
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ClinVar: RCV000007287
|
|
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|
|
|
</span>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Roelfsema et al. (2005) found a deletion of the first exon of the EP300 gene. It was considered probable that this deletion would lead to no expression from the affected allele. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, 1-BP DEL, 7100C
|
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|
<br />
|
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|
|
SNP: rs1569122847,
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|
|
ClinVar: RCV000007288, RCV003441707
|
|
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|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Zimmermann et al. (2007) identified a 1-bp deletion (7100delC) in exon 31 of the EP300 gene, The patient had a 'mild' form of the disorder with higher intelligence than other reported patients (IQ estimated at 75) and mild facial dysmorphism. The mutation is located close to the 3-prime end of the protein, was predicted to be a mild truncation, and does not alter the HAT domain. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, EX3-8DEL
|
|
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|
|
<br />
|
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|
|
|
ClinVar: RCV000007289
|
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with global developmental delay, slightly broad halluces but normal thumbs, and facial dysmorphism reminiscent of Rubinstein-Taybi syndrome-2 (RSTS2; 613684), especially while smiling, Foley et al. (2009) identified heterozygosity for a de novo deletion of exon 4 of the EP300 gene; RNA sequencing revealed that exon 2 was spliced to exon 9, indicating deletion of exons 3 through 8. Neither parent carried the deletion. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, 1-BP DEL, 638G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569090642,
|
|
|
|
|
|
|
|
ClinVar: RCV000023210
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-year-old boy with RSTS2 (RSTS2; 613684), Bartsch et al. (2010) identified an apparently de novo heterozygous 1-bp deletion (638delG) in exon 2 of the EP300 gene, predicted to result in a frameshift and premature termination. The child had severe microcephaly, retrognathia, broad thumbs and great toes, and delayed psychomotor development with marked speech delay. He also had posterior helical pits but normal palpebral fissures, nose, and mouth. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, 4-BP DEL, NT104
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886037664,
|
|
|
|
|
|
|
|
ClinVar: RCV000125469, RCV001175122, RCV002273956, RCV002477332
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old Caucasian boy with a phenotype overlapping Cornelia de Lange syndrome (122470), Woods et al. (2014) made the molecular diagnosis of RSTS2 (RSTS2; 613684) postmortem. Whole-exome sequencing identified a heterozygous c.104_107del mutation in exon 2 of the EP300 gene, resulting in a frameshift (Ser35fs). The mutation, which was confirmed by Sanger sequencing, was not found in either parent. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, PHE1595VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057517732,
|
|
|
|
|
|
|
|
ClinVar: RCV000414599, RCV000433095, RCV000509054, RCV000624116, RCV003401394
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hamilton et al. (2016) reported a 5-year-old girl (patient 5) with Rubinstein-Taybi syndrome (RSTS2; 613684) who was found by whole-exome sequencing as part of the Deciphering Developmental Disorders study (Firth et al., 2011) to have a de novo heterozygous c.4783T-G transversion (c.4783T-G, NM_001429.3) in the EP300 gene, resulting in a phe1595-to-val (F1595V) substitution at a highly conserved residue. Hamilton et al. (2016) confirmed the mutation by Sanger sequencing. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 RUBINSTEIN-TAYBI SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, ASN1286SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555910821,
|
|
|
|
|
|
|
|
ClinVar: RCV000439427, RCV001260706, RCV002244870, RCV002252119, RCV003401414
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By direct sequencing of the EP300 gene in a 2-year-old boy (patient 9) with typical features of Rubinstein-Taybi syndrome-2 (RSTS2; 613684), Hamilton et al. (2016) identified a de novo heterozygous c.3857A-G transition (c.3857-A-G, NM_001429.3), resulting in an asn1286-to-ser (N1286S) substitution at a highly conserved residue. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MENKE-HENNEKAM SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, GLN1824PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569120903,
|
|
|
|
|
|
|
|
ClinVar: RCV000757970, RCV003886433
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 17-year-old girl from the UK (patient E1) with Menke-Hennekam syndrome-2 (MKHK2; 618333), Menke et al. (2018) identified a heterozygous A-to-C transversion at nucleotide 5471 (c.5471A-C, NM_001429.3) in exon 31 of the EP300 gene, resulting in a glutamine-to-proline substitution at codon 1824 (Q1824P). This patient had been reported by Hamilton et al. (2016) as patient 6. Menke et al. (2018) and Hamilton et al. (2016) demonstrated that this mutation occurred as a de novo event. The Q1824P mutation was not found in the ESP or gnomAD databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MENKE-HENNEKAM SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EP300, 3-BP DEL, NT5492
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569120910,
|
|
|
|
|
|
|
|
ClinVar: RCV000757971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old girl from the Netherlands (patient E2) with Menke-Hennekam syndrome-2 (MKHK2; 618333), Menke et al. (2018) identified a heterozygous 3-basepair deletion in exon 31 of the EP300 gene (c.5492_5494del, NM_001429.3) that resulted in deletion of arginine-1831 (arg1831del). Menke et al. (2018) demonstrated that this mutation occurred as a de novo event. The arg1831del mutation was not found in the ESP or gnomAD databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
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|
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|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
An, W., Kim, J., Roeder, R. G.
|
|
<strong>Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.</strong>
|
|
Cell 117: 735-748, 2004.
|
|
|
|
|
|
[PubMed: 15186775]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2004.05.009]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arany, Z., Newsome, D., Oldread, E., Livingston, D. M., Eckner, R.
|
|
<strong>A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.</strong>
|
|
Nature 374: 81-84, 1995.
|
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|
|
[PubMed: 7870178]
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|
|
[Full Text: https://doi.org/10.1038/374081a0]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arany, Z., Sellers, W. R., Livingston, D. M., Eckner, R.
|
|
<strong>E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. (Letter)</strong>
|
|
Cell 77: 799-800, 1994.
|
|
|
|
|
|
[PubMed: 8004670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90127-9]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attanasio, C., Nord, A. S., Zhu, Y., Blow, M. J., Li, Z., Liberton, D. K., Morrison, H., Plajzer-Frick, I., Holt, A., Hosseini, R., Phouanenavong, S., Akiyama, J. A., Shoukry, M., Afzal, V., Rubin, E. M., FitzPatrick, D. R., Ren, B., Hallgrimsson, B., Pennacchio, L. A., Visel, A.
|
|
<strong>Fine tuning of craniofacial morphology by distant-acting enhancers.</strong>
|
|
Science 342: 1241006, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 24159046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1241006]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bartsch, O., Labonte, J., Albrecht, B., Wieczorek, D., Lechno, S., Zechner, U., Haaf, T.
|
|
<strong>Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome.</strong>
|
|
Am. J. Med. Genet. 152A: 181-184, 2010.
|
|
|
|
|
|
[PubMed: 20014264]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33153]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Das, C., Lucia, M. S., Hansen, K. C., Tyler, J. K.
|
|
<strong>CBP/p300-mediated acetylation of histone H3 on lysine56.</strong>
|
|
Nature 459: 113-117, 2009. Note: Erratum: Nature 460: 1164 only, 2009.
|
|
|
|
|
|
[PubMed: 19270680]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07861]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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<strong>Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1.</strong>
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Woods, S. A., Robinson, H. B., Kohler, L. J., Agamanolis, D., Sterbenz, G., Khalifa, M.
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<strong>Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.</strong>
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Xu, C.-R., Cole, P. A., Meyers, D. J., Kormish, J., Dent, S., Zaret, K. S.
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<strong>Chromatin 'prepattern' and histone modifiers in a fate choice for liver and pancreas.</strong>
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Yao, T. P., Oh, S. P., Fuchs, M., Zhou, N.-D., Ch'ng, L.-E., Newsome, D., Bronson, R. T., Li, E., Livingston, D. M., Eckner, R.
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<strong>Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.</strong>
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Zimmermann, N., Acosta, A. M. B. F., Kohlhase, J., Bartsch, O.
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Contributors:
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Ada Hamosh - updated : 02/26/2019<br>Ada Hamosh - updated : 02/22/2019<br>Cassandra L. Kniffin - updated : 11/15/2017<br>Michael Muriello - updated : 03/02/2017<br>Ada Hamosh - updated : 6/2/2015<br>Ada Hamosh - updated : 2/3/2014<br>Ada Hamosh - updated : 2/7/2013<br>Ada Hamosh - updated : 3/7/2012<br>Ada Hamosh - updated : 8/30/2011<br>Ada Hamosh - updated : 6/14/2011<br>Ada Hamosh - updated : 6/6/2011<br>Cassandra L. Kniffin - updated : 1/6/2011<br>Ada Hamosh - updated : 4/22/2010<br>Matthew B. Gross - updated : 3/8/2010<br>Patricia A. Hartz - updated : 12/8/2009<br>Marla J. F. O'Neill - updated : 10/30/2009<br>Ada Hamosh - updated : 9/9/2009<br>Ada Hamosh - updated : 5/19/2009<br>Ada Hamosh - updated : 3/9/2009<br>Ada Hamosh - updated : 11/26/2008<br>Ada Hamosh - updated : 3/20/2008<br>Cassandra L. Kniffin - updated : 8/13/2007<br>Ada Hamosh - updated : 1/30/2006<br>Victor A. McKusick - updated : 3/11/2005<br>Patricia A. Hartz - updated : 2/23/2005<br>Stylianos E. Antonarakis - updated : 8/5/2004<br>Ada Hamosh - updated : 4/22/2003<br>Ada Hamosh - updated : 2/21/2003<br>Ada Hamosh -updated : 11/12/2002<br>Stylianos E. Antonarakis - updated : 9/23/2002<br>Stylianos E. Antonarakis - updated : 11/5/2001<br>Stylianos E. Antonarakis - updated : 7/3/2001<br>Ada Hamosh - updated : 3/12/2001<br>Victor A. McKusick - updated : 3/1/2000<br>Patti M. Sherman - updated : 4/16/1999<br>Ada Hamosh - updated : 4/15/1999
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