PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.

PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
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DOI:
10.1038/nsmb.2700
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发表时间:
2013-11
影响因子:
16.8
通讯作者:
Bonasio, Roberto
Bonasio, Roberto
中科院分区:
生物学1区
文献类型:
--
作者:
Kaneko, Syuzo;Son, Jinsook;Shen, Steven S.;Reinberg, Danny;Bonasio, Roberto

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EZH 2是PRC 2的催化亚基,PRC 2是体内发育过程和体外胚胎干细胞(ESC)分化所必需的中央表观遗传阻遏物。PRC 2在沉积抑制性H3 K27 me 3标记中的生物化学功能已经很好地理解,但它如何在分化之前和分化期间被调节和定向到特定基因仍然未知。在这里,我们报告PRC 2在低水平下结合到小鼠ESC中的大多数启动子,包括许多有活性且缺乏H3 K27 me 3的启动子。使用体内RNA-蛋白质交联,我们表明EZH 2直接结合从这些启动子的子集转录的新生RNA的5′,并且这些结合事件与H3 K27 me 3减少相关。我们的研究结果表明PRC 2感知细胞转录状态并将其转化为表观遗传信息的分子机制。
EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27me3 marks is well understood, but how it is regulated and directed to specific genes before and during differentiation remains unknown. Here, we report that PRC2 binds at low levels to a majority of promoters in mouse ESCs, including many that are active and devoid of H3K27me3. Using in vivo RNA–protein crosslinking, we show that EZH2 directly binds to the 5′ of nascent RNAs transcribed from a subset of these promoters and that these binding events correlate with decreased H3K27me3. Our findings suggest a molecular mechanism by which PRC2 senses the transcriptional state of the cell and translates it into epigenetic information.
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