PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation.
PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation.
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DOI：
10.1126/science.aal2512
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发表时间：
2017-06-09
期刊：
影响因子：
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通讯作者：
Brockdorff N
中科院分区：
文献类型：
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作者：
Almeida M;Pintacuda G;Masui O;Koseki Y;Gdula M;Cerase A;Brown D;Mould A;Innocent C;Nakayama M;Schermelleh L;Nesterova TB;Koseki H;Brockdorff N
Xist RNA对Polycomb阻遏复合物PRC 1和PRC 2的募集是长链非编码RNA对染色质调控的重要范例。在这里，我们表明，非典型的PCGF 3/5-PRC 1复合物启动招聘PRC 1和PRC 2在响应Xist RNA表达。PCGF 3/5-PRC 1介导的组蛋白H2 A的泛素化信号募集其他非典型PRC 1复合物和PRC 2，导致组蛋白H3赖氨酸27甲基化染色体范围的沉积。Pcgf 3/5基因敲除导致雌性特异性胚胎致死，并消除了Xist介导的基因抑制，突出了Polycomb在Xist依赖的染色体沉默中的关键作用。我们的研究结果推翻了现有的Xist RNA Polycomb募集模型，并建立了H2 AK 119 u1在生理背景下启动Polycomb结构域形成的优先权。
Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long non-coding RNAs. Here we show that the non-canonical PCGF3/5-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1 mediated ubiquitylation of histone H2A signals recruitment of other non-canonical PRC1 complexes, and of PRC2, leading to deposition of histone H3 lysine 27 methylation chromosome wide. Pcgf3/5 gene knockout results in female specific embryo lethality, and abrogates Xist mediated gene repression, highlighting a key role for Polycomb in Xist dependent chromosome silencing. Our findings overturn existing models for Polycomb recruitment by Xist RNA, and moreover establish precedence for H2AK119u1 in initiating Polycomb domain formation in a physiological context.