Almeida Mafalda, Pintacuda Greta, Masui Osamu, Koseki Yoko, Gdula Michal, Cerase Andrea, Brown David, Mould Arne, Innocent Cassandravictoria, Nakayama Manabu, Schermelleh Lothar, Nesterova Tatyana B, Koseki Haruhiko, Brockdorff Neil
Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
Science. 2017 Jun 9;356(6342):1081-1084. doi: 10.1126/science.aal2512.
Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long noncoding RNAs. Here, we show that the noncanonical Polycomb group RING finger 3/5 (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 noncanonical PRC1 complexes and of PRC2, the latter leading to deposition of histone H3 lysine 27 methylation chromosome-wide. 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 establish precedence for H2AK119u1 in initiating Polycomb domain formation in a physiological context.
Xist RNA招募多梳抑制复合物PRC1和PRC2是长链非编码RNA对染色质进行调控的一个重要范例。在此，我们表明，非典型多梳家族RING指蛋白3/5（PCGF3/5）-PRC1复合物会响应Xist RNA的表达，启动PRC1和PRC2的招募。PCGF3/5-PRC1介导的组蛋白H2A泛素化标志着其他非典型PRC1复合物以及PRC2的招募，后者会导致全染色体范围的组蛋白H3赖氨酸27甲基化沉积。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，这突出了多梳蛋白在Xist依赖性染色体沉默中的关键作用。我们的研究结果推翻了现有关于Xist RNA招募多梳蛋白的模型，并为H2AK119u1在生理环境中启动多梳结构域形成建立了先例。
