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Review
. 2014 Feb 10:5:45.
doi: 10.3389/fimmu.2014.00045. eCollection 2014.

Function of YY1 in Long-Distance DNA Interactions

Michael L Atchison  1
Affiliations
Review

Function of YY1 in Long-Distance DNA Interactions

Michael L Atchison. Front Immunol. .

Abstract

During B cell development, long-distance DNA interactions are needed for V(D)J somatic rearrangement of the immunoglobulin (Ig) loci to produce functional Ig genes, and for class switch recombination (CSR) needed for antibody maturation. The tissue-specificity and developmental timing of these mechanisms is a subject of active investigation. A small number of factors are implicated in controlling Ig locus long-distance interactions including Pax5, Yin Yang 1 (YY1), EZH2, IKAROS, CTCF, cohesin, and condensin proteins. Here we will focus on the role of YY1 in controlling these mechanisms. YY1 is a multifunctional transcription factor involved in transcriptional activation and repression, X chromosome inactivation, Polycomb Group (PcG) protein DNA recruitment, and recruitment of proteins required for epigenetic modifications (acetylation, deacetylation, methylation, ubiquitination, sumoylation, etc.). YY1 conditional knock-out indicated that YY1 is required for B cell development, at least in part, by controlling long-distance DNA interactions at the immunoglobulin heavy chain and Igκ loci. Our recent data show that YY1 is also required for CSR. The mechanisms implicated in YY1 control of long-distance DNA interactions include controlling non-coding antisense RNA transcripts, recruitment of PcG proteins to DNA, and interaction with complexes involved in long-distance DNA interactions including the cohesin and condensin complexes. Though common rearrangement mechanisms operate at all Ig loci, their distinct temporal activation along with the ubiquitous nature of YY1 poses challenges for determining the specific mechanisms of YY1 function in these processes, and their regulation at the tissue-specific and B cell stage-specific level. The large numbers of post-translational modifications that control YY1 functions are possible candidates for regulation.

Keywords: DNA loops; YY1; cohesin; condensin; immunoglobulin loci; polycomb.

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Figures

Figure 1
Figure 1
Diagram of YY1 domains and functions. Domains of YY1 are indicated with specific functions listed. The regions of similarity to Drosophila Plieohomeotic are indicated below the diagram.
Figure 2
Figure 2
Immunoglobulin heavy chain locus diagram with V, D, J, and C regions indicated and locations of known YY1 binding sites, and the approximate positions of long-distance DNA loops that are YY1-dependent. The red circles represent the IgH intron and 3′RR enhancers. The left panel models rosette-like loops encompassing the VH regions at the pre–pro-B and pro-B cell stages. The right panel diagrams the Eμ-3′RR long-distance DNA loop required for CSR.
Figure 3
Figure 3
Igκ locus diagram showing the location of known YY1 binding sites, and the postulated YY1-dependent loops required for Vκ–Jκ rearrangement. Locations of the Igκ intron and κE3′ enhancers and shown by red circles and arrows. Postulated locus structure in pro-B and pre-B cells is show below.
Figure 4
Figure 4
Summary of protein co-localization data across the Igκ locus. The Igκ locus is shown in the top panel with Vκ genes represented by vertical lines. The identified YY1 binding sites are represented by black circles. Summary of ChIP data for YY1, EZH2, SMC4, SMC2, and BRRN1 are shown in the bottom panel. Positive ChIP signals are represented by a + symbol and question marks show inconclusive ChIP data.
Figure 5
Figure 5
Model of YY1 recruitment of proteins to DNA needed for long-distance DNA interactions. Using the IgH locus as a model, YY1 binding sites are indicated. Binding by YY1 then results in recruitment of condensin, cohesin, and PcG complex proteins. These proteins may form homotypic or heterotypic interactions to mediate long-distance DNA interactions. Positions of the Eμ enhancer, 3′RR enhancer, and various V genes are shown by arrows. Black rectangles represent various CH constant regions. YY1 also physically interacts with AID, and AID is able to interact with condensin, and cohesin complexes, and thus may contribute to DNA loop formation in germinal center B cells.
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