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

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.

Pubmed ID: 22068056


  • Forcales SV
  • Albini S
  • Giordani L
  • Malecova B
  • Cignolo L
  • Chernov A
  • Coutinho P
  • Saccone V
  • Consalvi S
  • Williams R
  • Wang K
  • Wu Z
  • Baranovskaya S
  • Miller A
  • Dilworth FJ
  • Puri PL


The EMBO journal

Publication Data

January 18, 2012

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR053779
  • Agency: NIAMS NIH HHS, Id: R01 AR052779
  • Agency: NIAMS NIH HHS, Id: R01 AR052779-06A1
  • Agency: NIAMS NIH HHS, Id: R01 AR056712
  • Agency: NIAMS NIH HHS, Id: R01 AR056712
  • Agency: NIAMS NIH HHS, Id: R01 AR056712-03
  • Agency: Telethon, Id: TCR05004

Mesh Terms

  • Animals
  • Cell Line
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA Helicases
  • Fibroblasts
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Multiprotein Complexes
  • Muscle Development
  • Muscle Proteins
  • MyoD Protein
  • Myoblasts
  • Nuclear Proteins
  • Phosphorylation
  • Phosphothreonine
  • Protein Processing, Post-Translational
  • RNA Interference
  • RNA, Small Interfering
  • Transcription Factors
  • Two-Hybrid System Techniques
  • p38 Mitogen-Activated Protein Kinases