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Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency

机译:乙酰化组蛋白H3K56与Oct4相互作用以促进小鼠胚胎干细胞多能性

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摘要

The presence of acetylated histone H3K56 (H3K56ac) in human ES cells (ESCs) correlates positively with the binding of Nanog, Sox2, and Oct4 (NSO) transcription factors at their target gene promoters. However, the function of H3K56ac there has been unclear. We now report that Oct4 interacts with H3K56ac in mouse ESC nuclear extracts and that perturbing H3K56 acetylation decreases Oct4–H3 binding. This interaction is likely to be direct because it can be recapitulated in vitro in an H3K56ac-dependent manner and is functionally important because H3K56ac combines with NSO factors in chromatin immunoprecipitation sequencing to mark the regions associated with pluripotency better than NSO alone. Moreover, reducing H3K56ac by short hairpin Asf1a decreases expression of pluripotency-related markers and increases expression of differentiation-related ones. Therefore, our data suggest that H3K56ac plays a central role in binding to Oct4 to promote the pluripotency of ESCs.
机译:人ES细胞(ESC)中乙酰化组蛋白H3K56(H3K56ac)的存在与Nanog,Sox2和Oct4(NSO)转录因子在其靶基因启动子上的结合正相关。但是,H3K56ac的功能尚不清楚。我们现在报道,Oct4与小鼠ESC核提取物中的H3K56ac相互作用,并且干扰H3K56的乙酰化作用会降低Oct4–H3的结合。这种相互作用可能是直接的,因为它可以以H3K56ac依赖性的方式在体外进行概括,并且在功能上很重要,因为H3K56ac与NSO因子结合在染色质免疫沉淀测序中,比单独的NSO更好地标记了多能性相关区域。此外,通过短发夹Asf1a降低H3K56ac会降低多能性相关标记的表达,并增加分化相关标记的表达。因此,我们的数据表明,H3K56ac在与Oct4结合以促进ESC的多能性中起着核心作用。

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