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Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation

Nature Genetics volume 27, pages 187–190 (2001)Cite this article

Abstract

Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression, cell-cycle control and oncogenesis1,2,3,4. MyoD is a muscle-specific regulator able to induce myogenesis in numerous cell types5. 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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Figure 1: Expression of dominant-negative BRG1 and BRM inhibits expression of muscle-specific gene expression during MyoD-mediated differentiation.
Figure 2: Retroviral insertion and expression of functional MyoD occurs in all differentiated samples.
Figure 3: Restriction endonuclease accessibility of the myogenin gene.

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Acknowledgements

We thank A. Lassar, B. Novitch and A. Javed for reagents and advice; R. Kingston for suggesting this line of experimentation; D. Edmondson and E. Olson for the myogenin genomic clone; S. Sif, L. Shopland, D. Hill, C. Guidi and C. Peterson for comments on the manuscript; and D. Hill and C. Baron for help with the figures. This work was supported by grants from the NIH to I.L.d.l.S. and A.N.I. and by a Scholar Award from the Leukemia and Lymphoma Society to A.N.I.

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  1. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Ivana L. de la Serna, Kerri A. Carlson & Anthony N. Imbalzano

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  1. Ivana L. de la Serna
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Correspondence to Anthony N. Imbalzano.

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de la Serna, I., Carlson, K. & Imbalzano, A. Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nat Genet 27, 187–190 (2001). https://doi.org/10.1038/84826

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