Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment

被引：257

作者：

Cooper, Sarah ^{[1
]}

Dienstbier, Martin ^{[2
]}

Hassan, Raihann ^{[1
]}

Schermelleh, Lothar ^{[1
]}

Sharif, Jafar ^{[3
]}

Blackledge, Neil P. ^{[1
]}

De Marco, Valeria ^{[4
]}

Elderkin, Sarah ^{[5
]}

Koseki, Haruhiko ^{[3
]}

Klose, Robert ^{[1
]}

Heger, Andreas ^{[2
]}

Brockdorff, Neil ^{[1
]}

机构：

[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England

[2] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, CGAT, Oxford OX1 3PT, England

[3] RIKEN Ctr Integrat Med Sci, Lab Dev Genet, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[4] MRC Natl Inst Med Res, The Ridgeway, London NW7 1AA, England

[5] Babraham Inst, Cambridge CB22 3AT, England

来源：

CELL REPORTS | 2014年 / 7卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

H3; LYSINE-27; METHYLATION; UBIQUITIN LIGASE COMPLEX; GROUP PROTEINS RING1A/B; DNA METHYLATION; CPG ISLANDS; HISTONE METHYLATION; X-INACTIVATION; H2A UBIQUITYLATION; BINDING-PROTEINS; PATERNAL GENOME;

D O I：

10.1016/j.celrep.2014.04.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs), CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications.

引用

页码：1456 / 1470

页数：15

共 74 条

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