Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation
Department of Cell Biology
Medical Subject Headings
Adenosine Triphosphatases; Animals; Cell Differentiation; DNA Helicases; Gene Expression Regulation; Mice; Muscles; MyoD Protein; Nuclear Proteins; Promoter Regions, Genetic; Transcription Factors
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.
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Citation: Nat Genet. 2001 Feb;27(2):187-90. Link to article on publisher's site