The BAF60c-MyoD complex poises chromatin for rapid transcription.

Chromatin remodeling by the SWI/SNF complex is required to activate the transcription of myogenic-specific genes. Our work addressed the details of how SWI/SNF is recruited to myogenic regulatory regions in response to differentiation signals. Surprisingly, the muscle determination factor MyoD and the SWI/SNF subunit BAF60c form a complex on the regulatory elements of MyoD-targeted genes in myogenic precursor cells. This Brg1-devoid MyoD-BAF60c complex flags the chromatin of myogenic-differentiation genes before transcription is activated. On differentiation, BAF60c phosphorylation on a conserved threonine by p38 α kinase promotes the incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD-target genes. Downregulation of BAF60c expression prevents MyoD access to the chromatin and the proper loading of an active myogenic transcriptosome preventing the expression of hundreds of myogenic genes. Our data support an unprecedented two-step model by which (1) pre-assembled BAF60c-MyoD complex poises the chromatin of myogenic genes for rapid transcription; (2) chromatin-bound BAF60c "senses" the myogenic differentiation cues and recruits an active SWI/SNF complex to remodel the chromatin allowing transcriptional activation.