Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex

Sonia V. Forcales, Sonia Albini, Lorenzo Giordani, Barbora Malecova, Luca Cignolo, Andrei Chernov, Paula Coutinho, Valentina Saccone, Silvia Consalvi, Roy Williams, Kepeng Wang, Zhenguo Wu, Svetlana Baranovskaya, Andrew Miller, F. Jeffrey Dilworth, Pier Lorenzo Puri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)301-316
Number of pages16
JournalEMBO Journal
Volume31
Issue number2
DOIs
Publication statusPublished - Jan 18 2012

Keywords

  • chromatin
  • gene expression
  • muscle differentiation
  • myod
  • p38

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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