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Signal‐dependent incorporation of MyoD–BAF60c into Brg1‐based SWI/SNF chromatin‐remodelling complex
Author(s) -
Forcales Sonia V,
Albini Sonia,
Giordani Lorenzo,
Malecova Barbora,
Cignolo Luca,
Chernov Andrei,
Coutinho Paula,
Saccone Valentina,
Consalvi Silvia,
Williams Roy,
Wang Kepeng,
Wu Zhenguo,
Baranovskaya Svetlana,
Miller Andrew,
Dilworth F Jeffrey,
Puri Pier Lorenzo
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.391
Subject(s) - swi/snf , biology , myod , smarca4 , chromatin remodeling , microbiology and biotechnology , genetics , chromatin , transcription factor , gene
Tissue‐specific transcriptional activators initiate differentiation towards specialized cell types by inducing chromatin modifications permissive for transcription at target loci, through the recruitment of SWItch/Sucrose NonFermentable (SWI/SNF) chromatin‐remodelling complex. However, the molecular mechanism that regulates SWI/SNF nuclear distribution in response to differentiation signals is unknown. We show that the muscle determination factor MyoD and the SWI/SNF subunit BAF60c interact on the regulatory elements of MyoD‐target genes in myoblasts, prior to activation of transcription. BAF60c facilitates MyoD binding to target genes and marks the chromatin for signal‐dependent recruitment of the SWI/SNF core to muscle genes. BAF60c phosphorylation on a conserved threonine by differentiation‐activated p38α kinase is the signal that promotes incorporation of MyoD–BAF60c into a Brg1‐based SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD‐target genes. Our data support an unprecedented two‐step model by which pre‐assembled BAF60c–MyoD complex directs recruitment of SWI/SNF to muscle loci in response to differentiation cues.