RYBP-PRC1 Complexes Mediate H2A Ubiquitylation at Polycomb Target Sites Independently of PRC2 and H3K27me3

Lígia Tavares,Emilia Dimitrova,David Oxley,Judith Webster,Raymond Poot,Jeroen Demmers,Karel Bezstarosti,Stephen Taylor,Hiroki Ura,Hiroshi Koide,Anton Wutz,Miguel Vidal,Sarah Elderkin,Neil Brockdorff

doi:10.1016/j.cell.2011.12.029

Abstract

SummaryPolycomb-repressive complex 1 (PRC1) has a central role in the regulation of heritable gene silencing during differentiation and development. PRC1 recruitment is generally attributed to interaction of the chromodomain of the core protein Polycomb with trimethyl histone H3K27 (H3K27me3), catalyzed by a second complex, PRC2. Unexpectedly we find that RING1B, the catalytic subunit of PRC1, and associated monoubiquitylation of histone H2A are targeted to closely overlapping sites in wild-type and PRC2-deficient mouse embryonic stem cells (mESCs), demonstrating an H3K27me3-independent pathway for recruitment of PRC1 activity. We show that this pathway is mediated by RYBP-PRC1, a complex comprising catalytic subunits of PRC1 and the protein RYBP. RYBP-PRC1 is recruited to target loci in mESCs and is also involved in Xist RNA-mediated silencing, the latter suggesting a wider role in Polycomb silencing. We discuss the implications of these findings for understanding recruitment and function of Polycomb repressors.

Highlights

Polycomb-group (PcG) repressor proteins play a key role in establishing and maintaining gene expression patterns during cellular differentiation and development
H2AK119u1 and Polycomb-repressive complex 1 (PRC1) Subunits Localize to PcG Target Genes in EedÀ/À ESCs To investigate the importance of H3K27me3 in PRC1 recruitment in mouse embryonic stem cells (mESCs), we performed ChIP for selected PcG target loci in EedÀ/À mESCs that lack H3K27me3
In addition to loci repressed by PcG proteins, we analyzed loci that are expressed in mESCs, loci that are widely expressed, and a locus that is repressed in mESCs independently of PcG activity

Summary

Introduction

Polycomb-group (PcG) repressor proteins play a key role in establishing and maintaining gene expression patterns during cellular differentiation and development. Co-occupancy is thought to be a consequence of recruitment of PRC1 via interaction of the chromodomain in the PRC1 protein PC (mammalian homologs CBX2/4/6/7/8) with PRC2-dependent H3K27me. Co-occupancy is thought to be a consequence of recruitment of PRC1 via interaction of the chromodomain in the PRC1 protein PC (mammalian homologs CBX2/4/6/7/8) with PRC2-dependent H3K27me3 This is based on biochemical studies demonstrating binding of the PC chromodomain to H3K27me (Cao et al, 2002; Fischle et al, 2003; Min et al, 2003) and on genetic analyses demonstrating displacement of PRC1 proteins from chromatin in PRC2 mutants (Boyer et al, 2006; Cao et al, 2002; Wang et al, 2004). The idea has been further substantiated in studies demonstrating a direct link between H3K27me and PRC1 recruitment (Agger et al, 2007; Lee et al, 2007; Mujtaba et al, 2008)

Results

Discussion

Conclusion