Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation

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(1-4) MyoD is a muscle-specific regulator able to in duce myogenesis in numerous cell types(5). To ascertain the requirement for chromatin remodeling enzymes in cellular differentiation processes, we exa mined MyoD-mediated induction of muscle differentiation in fibroblasts expr essing 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 chr omatin remodeling in the promoter region of an endogenous muscle-specific g ene. Our results demonstrate that SWI/SNF enzymes promote MyoD-mediated mus cle differentiation and indicate that these enzymes function by altering ch romatin structure in promoter regions of endogenous, differentiation-specif ic loci.