Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment.
Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment.
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DOI：
10.1016/j.celrep.2014.04.012
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发表时间：
2014-06-12
期刊：
影响因子：
8.8
通讯作者：
Brockdorff N
中科院分区：
文献类型：
--
作者：
Cooper S;Dienstbier M;Hassan R;Schermelleh L;Sharif J;Blackledge NP;De Marco V;Elderkin S;Koseki H;Klose R;Heger A;Brockdorff N
主要的Polycomb组（PcG）复合物PRC1和PRC2被募集到脊椎动物细胞中的靶位点的机制还没有很好地理解。基于最近的研究，确定DNA甲基化和Polycomb活性之间的相互关系，我们证明，在甲基化缺陷的胚胎干细胞（ESC），CpG密度结合拮抗作用的H3K9me3和H3K36me3重定向PcG复合物的臂间异染色质和基因丰富的域。令人惊讶的是，我们发现，PRC1连接的H2A单泛素化是足以招募PRC2的染色质在体内，这表明通过识别未甲基化的CpG决定的本地化的PRC1和PRC2在典型和非典型的目标网站的机制。我们讨论了我们的数据，新出现的证据表明，PcG招聘是一个默认状态，在许可的染色质位点，介导的CpG低甲基化和抵消H3尾修饰之间的相互作用。DNA甲基化的缺乏将Polycomb复合物募集到臂间异染色质H3K9me3拮抗PRC 2的活性，但不拮抗PRC 1，在臂间异染色质CpG密度和H3修饰的拮抗作用定义了全基因组Polycomb占据PRC 1介导的H2AK119u1募集PRC 2和H3K27me3 Polycomb组蛋白是发育调节基因的重要阻遏物，但是这些复合物如何被募集到它们的靶基因中仍然是未知的。在这项研究中，库珀等人。表明Polycomb组蛋白募集是未甲基化CpG密度和特定组蛋白尾部修饰的拮抗作用的组合读出。出乎意料的是，他们还表明，由Polycomb阻遏物复合物1（PRC1）产生的单泛素化组蛋白H2A足以招募PRC2。
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. Absence of DNA methylation recruits Polycomb complexes to pericentric heterochromatin H3K9me3 antagonizes activity of PRC2, but not PRC1, at pericentric heterochromatin CpG density and antagonism by H3 modifications define genome-wide Polycomb occupancy PRC1-mediated H2AK119u1 recruits PRC2 and H3K27me3 Polycomb group proteins are important repressors of developmentally regulated genes, but how these complexes are recruited to their target genes is still largely unknown. In this study, Cooper et al. show that Polycomb group protein recruitment is a combinatorial readout of unmethylated CpG density and antagonism by specific histone tail modifications. Unexpectedly, they also show that monoubiquitylated histone H2A, the modification produced by Polycomb repressor complex 1 (PRC1), is sufficient to recruit PRC2.
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影响因子：
16
作者：
Blackledge NP;Zhou JC;Tolstorukov MY;Farcas AM;Park PJ;Klose RJ
通讯作者：
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影响因子：
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通讯作者：
Koseki, H
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通讯作者：
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