Ago1 controls myogenic differentiation by regulating eRNA-mediated CBP-guided epigenome reprogramming.

Bodor Fallatah, Muhammad Shuaib, Sabir Adroub, Andreu Paytuví-Gallart, Francesco Della Valle, Seba Nadeef, Chiara Lanzuolo, Valerio Orlando

Cell reports 2021 Nov 30

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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. Copyright © 2021 King Abdullah University of Science and Technology. Published by Elsevier Inc. All rights reserved.

Citation

Bodor Fallatah, Muhammad Shuaib, Sabir Adroub, Andreu Paytuví-Gallart, Francesco Della Valle, Seba Nadeef, Chiara Lanzuolo, Valerio Orlando. Ago1 controls myogenic differentiation by regulating eRNA-mediated CBP-guided epigenome reprogramming. Cell reports. 2021 Nov 30;37(9):110066