RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3.
RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3.
复制标题
DOI：
10.1016/j.cell.2011.12.029
复制
发表时间：
2012-02-17
期刊：
影响因子：
64.5
通讯作者：
Brockdorff N
中科院分区：
文献类型：
--
作者：
Tavares L;Dimitrova E;Oxley D;Webster J;Poot R;Demmers J;Bezstarosti K;Taylor S;Ura H;Koide H;Wutz A;Vidal M;Elderkin S;Brockdorff N
多梳抑制复合物1（PRC 1）在分化和发育过程中调节遗传性基因沉默中起着重要作用。PRC 1募集通常归因于核心蛋白Polycomb的染色体结构域与三甲基组蛋白H3 K27（H3 K27 me 3）的相互作用，由第二复合物PRC 2催化。出乎意料的是，我们发现RING 1B，PRC 1的催化亚基，以及相关的组蛋白H2 A的单泛素化被靶向到野生型和PRC 2缺陷小鼠胚胎干细胞（mESC）中的紧密重叠位点，证明了PRC 1活性募集的H3 K27 me 3独立途径。我们表明，这一途径是介导的RYBP-PRC 1，一个复杂的催化亚基PRC 1和蛋白质RYBP。RYBP-PRC 1被募集到mESC中的靶位点，并且还参与Xist RNA介导的沉默，后者表明在Polycomb沉默中具有更广泛的作用。我们讨论了这些研究结果的意义，了解招聘和功能的Polycomb抑制剂。在不存在H3 K27 me 3的情况下，在Polycomb靶基因座处保留了H3 K27 me 3泛素化。介导的H2 A泛素化蛋白RYBP-PRC 1定位于Polycomb靶位点，独立于H3 K27 me 3蛋白RYBP-PRC 1是维持mESC中全局H2 AK 119 u1所必需的一种新鉴定的含有RYBP亚基的PRC 1复合物变体允许PRC 1起作用独立于PRC 2。这种替代复合物对于维持胚胎干细胞和失活X染色体上的适当染色质状态非常重要。
Polycomb-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. ► H2A ubiquitylation is retained at Polycomb target loci in the absence of H3K27me3 ► Mutually exclusive complexes, CBX-PRC1 and RYBP-PRC1, mediate H2A ubiquitylation ► RYBP-PRC1 localizes to Polycomb target sites independent of H3K27me3 ► RYBP-PRC1 is required for maintenance of global H2AK119u1 in mESCs A newly identified variant of the PRC1 complex containing the RYBP subunit allows PRC1 to act independently of PRC2. This alternative complex is important for maintaining the proper chromatin state in ESCs and on the inactive X chromosome.
登录
查看更多内容
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
21.3
作者：
Hansen, Klaus H.;Bracken, Adrian P.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
2.9
作者：
Czypionka, Anna;Paños, Olga Ruiz De Los;Neira, José L.
通讯作者：
Neira, José L.
影响因子：
3
作者：
Huen, David S.;Russell, Steven
通讯作者：
Russell, Steven