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The PRC2-associated factor C17orf96 is a novel CpG island regulator in mouse ES cells

机译:PRC2相关因子C17orf96是小鼠ES细胞中的新型CpG岛调控因子

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CpG islands (CGIs) are key DNA regulatory elements in the vertebrate genome and are often found at gene promoters. In mammalian embryonic stem (ES) cells, CGIs are decorated by either the active or repressive histone marks, H3K4me3 and H3K27me3, respectively, or by both modifications (‘bivalent domains’), but their precise regulation is incompletely understood. Remarkably, we find that the polycomb repressive complex 2 (PRC2)-associated protein C17orf96 (a.k.a. esPRC2p48 and E130012A19Rik) is present at most CGIs in mouse ES cells. At PRC2-rich CGIs, loss of C17orf96 results in an increased chromatin binding of Suz12 and elevated H3K27me3 levels concomitant with gene repression. In contrast, at PRC2-poor CGIs, located at actively transcribed genes, C17orf96 colocalizes with RNA polymerase II and its depletion leads to a focusing of H3K4me3 in the core of CGIs. Our findings thus identify C17orf96 as a novel context-dependent CGI regulator.
机译:CpG岛(CGI)是脊椎动物基因组中的关键DNA调控元件,通常在基因启动子处发现。在哺乳动物胚胎干(ES)细胞中,CGIs分别通过活性或抑制性组蛋白标记H3K4me3和H3K27me3或通过两种修饰(“二价域”)修饰,但它们的精确调控尚不完全清楚。值得注意的是,我们发现在小鼠ES细胞中的大多数CGI中都存在与多梳抑制复合物2(PRC2)相关的蛋白C17orf96(也称为esPRC2p48和E130012A19Rik)。在富含PRC2的CGI处,C17orf96的缺失导致Suz12的染色质结合增加,H3K27me3水平升高,并伴随基因阻抑。相反,在PRC2缺失的CGI处,位于活跃转录的基因处,C17orf96与RNA聚合酶II共定位,其消耗导致H3K4me3集中在CGI的核心中。因此,我们的发现将C17orf96识别为一种新型的上下文相关CGI调节剂。

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