Authors: Bodor Fallatah, Muhammad Shuaib, Sabir Adroub, Andreu Paytuví-Gallart, Francesco Della Valle, Seba Nadeef, ChiaraLanzuolo, Valerio Orlando
- King Abdullah University of Science and Technology, KAUST Environmental Epigenetics Research Program, Biological and Environmental Sciences and Engineering Division, Thuwal 23955, Saudi Arabia
- Sequentia Biotech, Carrer Comte D’Urgell 240, 08036 Barcelona, Spain
- Institute of Biomedical Technologies, National Research Council, 20090 Milan, Italy
- National Institute of Molecular Genetics (INGM) “Romeo ed Enrica Invernizzi,” Chromatin and Nuclear Architecture Laboratory, 20122 Milan, Italy
Publication: Cell Reports
Date: November 2021
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.