Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.

Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.
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DOI:
10.1016/j.stem.2011.12.017
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发表时间:
2012-02-03
期刊:
影响因子:
23.9
通讯作者:
Pombo, Ana
Pombo, Ana
中科院分区:
医学1区
文献类型:
--
作者:
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana

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多角膜复制品(PRC)是重要的染色质修饰剂,在多能性和癌症中实现了胚胎干细胞中的多孔沉默(ESC)。全基因组。 PRC目标首先显示出一系列RNAPII变体,由非生产性的RNAPII(S5P+S7P-S2P-)结合。在物理上结合相同的染色质,并在功能上结合。 (S5P+S7P+S2P+)它们产生mRNA和蛋白质,它们的表达在PRC1敲低时增加。 。 ►独特的RNAPII变体(S5P+S7P-S2P-)结合PRC目标在ESCS中跨基因组►RNAPII-S5P和PRC在时间和本地化中重合,并且显示出比例丰度►显示新颖的,活跃的PRC-TARGET基因基因►主动PRC目标在ESC人群中开/关(Active/Prc)状态之间切换
Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p+S7p−S2p−) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p+S7p+S2p+); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism. ► A unique RNAPII variant (S5p+S7p−S2p−) binds PRC targets genome-wide in ESCs ► RNAPII-S5p and PRC coincide in time and localization, and show proportional abundance ► Novel, active PRC-target genes identified in ESCs include metabolic genes ► Active PRC targets switch between on/off (active/PRC) states in the ESC population
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