Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jun 30;429(13):1934-1945.
doi: 10.1016/j.jmb.2016.11.019. Epub 2016 Nov 26.

The Histone Variant H3.3 in Transcriptional Regulation and Human Disease

Leilei Shi  1 , Hong Wen  1 , Xiaobing Shi  2
Affiliations
Review

The Histone Variant H3.3 in Transcriptional Regulation and Human Disease

Leilei Shi et al. J Mol Biol. .

Abstract

Histone proteins wrap around DNA to form nucleosomes, which further compact into the higher-order structure of chromatin. In addition to the canonical histones, there are also variant histones that often have pivotal roles in regulating chromatin dynamics and in the accessibility of the underlying DNA. H3.3 is the most common non-centromeric variant of histone H3 that differs from the canonical H3 by just 4-5 aa. Here, we discuss the current knowledge of H3.3 in transcriptional regulation and the recent discoveries and molecular mechanisms of H3.3 mutations in human cancer.

Keywords: DAXX; H3.3; HIRA; epigenetics; human cancer.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Protein sequence, genomic distributions, and cancer mutations of H3.3
Amino acids in H3.3 that are distinct from canonical H3 are shown in blue squares and highlighted with residue numbers. G90 is an essential amino acid recognized by UBN1 in the HIRA complex or DAXX in the DAXX/ATRX, the two known variant-specific chaperones that deposit H3.3 into distinct chromosomal regions that is highlighted in different colors in the schematic representation of chromosome. Amino acids that are mutated in human cancers are shown in red squares and highlighted with residue numbers. Mutation of K27M or K36M inhibits the enzymatic activity of EZH2 or SETD2, respectively, leading to global loss of H3K27 methylation in DIPG or H3K36 methylation in chondroblastoma. The mechanism of G34 mutations to various amino acids is current not clear. Abbreviations: A: alanine; G: glycine; I: isoleucine; K: lysine; L: leucine; M: methionine; R: arginine; S: serine; DIPG: diffuse intrinsic pontine glioma; GCTB: giant cell tumors of the bone; GBM: glioblastoma.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 angstrom resolution. Nature. 1997;389:251–60. - PubMed
    1. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–5. - PubMed
    1. Hake SB, Allis CD. Histone H3 variants and their potential role in indexing mammalian genomes: The “H3 barcode hypothesis”. P Natl Acad Sci USA. 2006;103:6428–35. - PMC - PubMed
    1. Szenker E, Ray-Gallet D, Almouzni G. The double face of the histone variant H3.3. Cell Research. 2011;21:421–34. - PMC - PubMed
    1. Skene PJ, Henikoff S. Histone variants in pluripotency and disease. Development (Cambridge, England) 2013;140:2513–24. - PubMed

Publication types

LinkOut - more resources