MyoD公司
增强子
细胞生物学
生物
染色质
肌发生
基因表达调控
五年期
表观基因组
基因表达
遗传学
基因
心肌细胞
DNA甲基化
作者
Bodor Fallatah,Muhammad Shuaib,Sabir A. Adroub,Andreu Paytuví-Gallart,Francesco Della Valle,Seba Nadeef,Chiara Lanzuolo,Valerio Orlando
出处
期刊:Cell Reports
[Elsevier]
日期:2021-11-01
卷期号:37 (9): 110066-110066
被引量:11
标识
DOI:10.1016/j.celrep.2021.110066
摘要
The role of chromatin-associated RNAi components in the nucleus of mammalian cells and in particular in the context of developmental programs remains to be elucidated. Here, we investigate the function of nuclear Argonaute 1 (Ago1) in gene expression regulation during skeletal muscle differentiation. We show that Ago1 is required for activation of the myogenic program by supporting chromatin modification mediated by developmental enhancer activation. Mechanistically, we demonstrate that Ago1 directly controls global H3K27 acetylation (H3K27ac) by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction, a key step in enhancer-driven gene activation. In particular, we show that Ago1 is specifically required for myogenic differentiation 1 (MyoD) and downstream myogenic gene activation, whereas its depletion leads to failure of CBP acetyltransferase activation and blocking of the myogenic program. Our work establishes a role of the mammalian enhancer-associated RNAi component Ago1 in epigenome regulation and activation of developmental programs.
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