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. 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.
de la Serna
I L
IL
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Carlson
K A
KA
Imbalzano
A N
AN
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D004265:DNA Helicases; D005786:Gene Expression Regulation; D051379:Mice; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017570:MyoD Protein; D009687:Nuclear Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases