Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation

Nat Genet. 2001 Feb;27(2):187-90. doi: 10.1038/84826.


Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression, cell-cycle control and oncogenesis. MyoD is a muscle-specific regulator able to induce myogenesis in numerous cell types. To ascertain the requirement for chromatin remodeling enzymes in cellular differentiation processes, we examined MyoD-mediated induction of muscle differentiation in fibroblasts expressing dominant-negative versions of the human brahma-related gene-1 (BRG1) or human brahma (BRM), the ATPase subunits of two distinct SWI/SNF enzymes. We find that induction of the myogenic phenotype is completely abrogated in the presence of the mutant enzymes. We further demonstrate that failure to induce muscle-specific gene expression correlates with inhibition of chromatin remodeling in the promoter region of an endogenous muscle-specific gene. Our results demonstrate that SWI/SNF enzymes promote MyoD-mediated muscle differentiation and indicate that these enzymes function by altering chromatin structure in promoter regions of endogenous, differentiation-specific loci.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cell Differentiation
  • DNA Helicases
  • Gene Expression Regulation
  • Mice
  • Muscles / cytology*
  • MyoD Protein / genetics
  • MyoD Protein / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • MyoD Protein
  • Nuclear Proteins
  • Transcription Factors
  • Adenosine Triphosphatases
  • Smarca4 protein, mouse
  • DNA Helicases