心理压抑
生物
多组蛋白
染色质
基因沉默
遗传学
基因
基因表达调控
PRC2
细胞生物学
基因表达
抑制因子
组蛋白H3
作者
Nadezda A. Fursova,Neil P. Blackledge,Manabu Nakayama,Shinsuke Ito,Yoko Koseki,Anca M. Farcas,Hamish W. King,Haruhiko Koseki,Robert J. Klose
出处
期刊:Molecular Cell
[Elsevier BV]
日期:2019-04-24
卷期号:74 (5): 1020-1036.e8
被引量:246
标识
DOI:10.1016/j.molcel.2019.03.024
摘要
The Polycomb system modifies chromatin and plays an essential role in repressing gene expression to control normal mammalian development. However, the components and mechanisms that define how Polycomb protein complexes achieve this remain enigmatic. Here, we use combinatorial genetic perturbation coupled with quantitative genomics to discover the central determinants of Polycomb-mediated gene repression in mouse embryonic stem cells. We demonstrate that canonical Polycomb repressive complex 1 (PRC1), which mediates higher-order chromatin structures, contributes little to gene repression. Instead, we uncover an unexpectedly high degree of synergy between variant PRC1 complexes, which is fundamental to gene repression. We further demonstrate that variant PRC1 complexes are responsible for distinct pools of H2A monoubiquitylation that are associated with repression of Polycomb target genes and silencing during X chromosome inactivation. Together, these discoveries reveal a new variant PRC1-dependent logic for Polycomb-mediated gene repression.
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