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Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation
I L de la Serna1, K A Carlson, A N Imbalzano
1Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Nature Genetics
|February 15, 2001
Summary
Mammalian SWI/SNF enzymes are crucial for muscle cell differentiation. These chromatin remodelers, including Brahma-related gene-1 (BRG1) and Brahma (BRM), are required for MyoD-induced myogenesis and gene expression.
Area of Science:
- Cellular and Molecular Biology
- Epigenetics and Gene Regulation
Background:
- SWI/SNF complexes are ATP-dependent chromatin remodelers involved in gene expression, cell cycle, and cancer.
- MyoD is a key muscle-specific transcription factor that drives myogenesis.
Purpose of the Study:
- To investigate the role of SWI/SNF chromatin remodeling enzymes in MyoD-mediated muscle differentiation.
- To determine if SWI/SNF activity is essential for inducing the myogenic phenotype and muscle-specific gene expression.
Main Methods:
- Used dominant-negative versions of human Brahma-related gene-1 (BRG1) and human Brahma (BRM) in fibroblasts.
- Examined MyoD-induced muscle differentiation and muscle-specific gene expression.
- Assessed chromatin remodeling at the promoter of an endogenous muscle-specific gene.
Main Results:
- MyoD-induced muscle differentiation was completely blocked by dominant-negative BRG1 or BRM.
- Inhibition of SWI/SNF enzymes prevented muscle-specific gene expression.
- Chromatin remodeling at muscle-specific gene promoters was inhibited in the presence of mutant SWI/SNF enzymes.
Conclusions:
- SWI/SNF enzymes, specifically BRG1 and BRM, are essential for MyoD-mediated muscle differentiation.
- These chromatin remodelers function by modifying chromatin structure at the promoter regions of differentiation-specific genes.
- Chromatin remodeling is a critical step in the process of cellular differentiation.