University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Imbalzano Lab

Publication Date


Document Type

Article Preprint


Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes | Molecular Biology | Musculoskeletal, Neural, and Ocular Physiology


Skeletal muscle differentiation induces changes in the epigenome of myoblasts as they proceed towards a myogenic phenotype. mSWI/SNF chromatin remodeling enzymes coordinate with lineage-determining transcription factors and are key regulators of differentiation. Three mSWI/SNF proteins, the mutually exclusive ATPases, BRG1 and BRM, and the BAF180 protein (Polybromo1, PBRM1) contain bromodomains belonging to the same structural subfamily. Bromodomains bind to acetylated lysines on histone N-terminal tails and on other proteins. Pharmacological inhibition of mSWI/SNF bromodomain function using the selective inhibitor PFI-3 reduced differentiation, decreased expression of myogenic genes, and increased the expression of cell cycle-related genes and the number of cells that remained in the cell cycle. Knockdown of BAF180 had no effect on differentiation, suggesting that only the BRG1 and BRM bromodomains contributed to differentiation. Comparison with existing gene expression data from myoblasts subjected to knockdown of BRG1 or BRM showed that bromodomain function was required for a subset of BRG1- and BRM-dependent gene expression. ChIP analysis revealed decreased BRG1 and BRM binding to target gene promoters, indicating that the BRG1 and BRM bromodomains promote chromatin binding. Thus mSWI/SNF ATPase bromodomains contribute to cell cycle exit, to skeletal muscle-specific gene expression, and to stable promoter binding by the mSWI/SNF ATPases.


Molecular Biology, Bromodomains, Skeletal muscle, enzymes

Rights and Permissions

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.

DOI of Published Version



bioRxiv 2020.08.25.267666; doi: Link to preprint on bioRxiv service.

Journal/Book/Conference Title


Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License