The Mll2 branch of the COMPASS family regulates bivalent promoters in mouse embryonic stem cells.

The Mll2 branch of the COMPASS family regulates bivalent promoters in mouse embryonic stem cells.
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DOI:
10.1038/nsmb.2653
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发表时间:
2013-09
影响因子:
16.8
通讯作者:
Shilatifard A
Shilatifard A
中科院分区:
生物学1区
文献类型:
--
作者:
Hu D;Garruss AS;Gao X;Morgan MA;Cook M;Smith ER;Shilatifard A

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许多发育调控基因的启动子在胚胎干细胞状态下具有H3K27me3和H3K4me3的二价标记,这被认为是在分化过程中赋予精确的时间激活。虽然已知Polycomb抑制复合体2 (PRC2)执行H3K27me3,但在二价标记启动子中负责H3K4me3的COMPASS家族成员以前是未知的。在这里,我们发现Mll2 (KMT2b)是在胚胎干细胞双价标记启动子上负责H3K4me3的酶。虽然双价基因上的H3K4me3被认为可以启动未来的激活,但在Mll2缺失的细胞中,我们没有发现维甲酸处理后快速转录诱导的实质性缺陷。我们鉴定出Mll2复合体是COMPASS家族成员,负责在二价启动子处实现H3K4me3,这为重新评估和实验测试二价在胚胎干细胞状态和分化中的功能模型提供了机会。
Promoters of many developmentally regulated genes have a bivalent mark of H3K27me3 and H3K4me3 in embryonic stem cells state, which is proposed to confer precise temporal activation upon differentiation. Although Polycomb repressive complex 2 (PRC2) is known to implement H3K27me3, the COMPASS family member responsible for H3K4me3 at bivalently-marked promoters was previously unknown. Here, we identify Mll2 (KMT2b) as the enzyme responsible for H3K4me3 on bivalently-marked promoters in embryonic stem cells. Although H3K4me3 at bivalent genes is proposed to prime future activation, we did not detect a substantial defect in rapid transcriptional induction after retinoic acid treatment in Mll2 depleted cells. Our identification of the Mll2 complex as the COMPASS family member responsible for implementing H3K4me3 at bivalent promoters provides an opportunity to reevaluate and experimentally test models for the function of bivalency in the embryonic stem cell state and in differentiation.
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