Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation

• Published in: Nature genetics Vol. 27; no. 2; pp. 187 - 190
• Main Authors: Imbalzano, Anthony N, de la Serna, Ivana L, Carlson, Kerri A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.02.2001
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Animals; Antibodies; ATP; Biological and medical sciences; Brahma gene; brahma-related gene-1; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Control; DNA binding proteins; DNA Helicases; Enzymes; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genetic aspects; Kinases; Mammals; Mice; Molecular and cellular biology; Muscle diseases; Muscles - cytology; MyoD protein; MyoD Protein - genetics; MyoD Protein - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Physiological aspects; Promoter Regions, Genetic; Proteins; Publishing; SWI/SNF complex; Transcription Factors - genetics; Transcription Factors - metabolism; United States; Cell culture; Vertebrata; Regulation(control); Cell line; Mammalia; Gene; Molecular complex; Muscle; Cell differentiation; Gene expression; Transcription factor MyoD
• ISSN: 1061-4036; 1546-1718
• 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.