Nascent RNA interaction keeps PRC2 activity poised and in check.

Nascent RNA interaction keeps PRC2 activity poised and in check.
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DOI:
10.1101/gad.247940.114
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发表时间:
2014-09-15
影响因子:
10.5
通讯作者:
Reinberg D
Reinberg D
中科院分区:
生物学1区
文献类型:
--
作者:
Kaneko S;Son J;Bonasio R;Shen SS;Reinberg D

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polycomb - repression complex 2 (PRC2)定位于抑制基因的启动子区域,产生H3K27me2/3,但也定位于胚胎干细胞中缺乏H3K27me2/3的活性基因的新生转录本。Kaneko等人表明,RNA相互作用抑制含有SET结构域的蛋白,如PRC2。crispr介导的截断prc2相互作用的新生RNA挽救了prc2介导的H3K27me2/3沉积。这项研究支持了一个模型,即PRC2只能标记那些被转录抑制物沉默的基因的抑制。polycomb - suppression complex 2 (PRC2)通过在Lys27位点(H3K27me2/3)催化组蛋白H3的甲基化,促进抑制转录的染色质结构域的维持和遗传。然而,通过其EZH2亚基,PRC2也可以结合胚胎干细胞中缺乏H3K27me2/3的活性基因的新生转录物。这里,生化分析表明,RNA相互作用在体外非特异性地抑制含有SET结构域的蛋白,如PRC2。然而,crispr介导的截断prc2相互作用的新生RNA挽救了prc2介导的H3K27me2/3沉积。与新生转录物的相互作用抑制了PRC2的活性,这支持了一种模型,即PRC2只能标记那些被转录抑制物沉默的基因。
Polycomb-repressive complex 2 (PRC2) localizes to the promoter regions of repressed genes giving rise to H3K27me2/3 but also localizes to nascent transcripts from active genes that are devoid of H3K27me2/3 in embryonic stem cells. Kaneko et al. show that RNA interaction inhibits SET domain-containing proteins, such as PRC2. CRISPR-mediated truncation of a PRC2-interacting nascent RNA rescued PRC2-mediated deposition of H3K27me2/3. This study supports a model in which PRC2 can only mark for repression those genes silenced by transcriptional repressors. Polycomb-repressive complex 2 (PRC2) facilitates the maintenance and inheritance of chromatin domains repressive to transcription through catalysis of methylation of histone H3 at Lys27 (H3K27me2/3). However, through its EZH2 subunit, PRC2 also binds to nascent transcripts from active genes that are devoid of H3K27me2/3 in embryonic stem cells. Here, biochemical analyses indicated that RNA interaction inhibits SET domain-containing proteins, such as PRC2, nonspecifically in vitro. However, CRISPR-mediated truncation of a PRC2-interacting nascent RNA rescued PRC2-mediated deposition of H3K27me2/3. That PRC2 activity is inhibited by interactions with nascent transcripts supports a model in which PRC2 can only mark for repression those genes silenced by transcriptional repressors.
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