Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis

Sonia Albini, Paula Coutinho Toto, Alessandra Dall'Agnese, Barbora Malecova, Carlo Cenciarelli, Armando Felsani, Maurizia Caruso, Scott J. Bultman, Pier Lorenzo Puri

Research output: Contribution to journalArticle

Abstract

Although the two catalytic subunits of the SWI/SNF chromatin-remodeling complex - Brahma (Brm) and Brg1 - are almost invariably co-expressed, their mutually exclusive incorporation into distinct SWI/SNF complexes predicts that Brg1- and Brm-based SWI/SNF complexes execute specific functions. Here, we show that Brg1 and Brm have distinct functions at discrete stages of muscle differentiation. While Brg1 is required for the activation of muscle gene transcription at early stages of differentiation, Brm is required for Ccnd1 repression and cell cycle arrest prior to the activation of muscle genes. Ccnd1 knockdown rescues the ability to exit the cell cycle in Brm-deficient myoblasts, but does not recover terminal differentiation, revealing a previously unrecognized role of Brm in the activation of late muscle gene expression independent from the control of cell cycle. Consistently, Brm null mice displayed impaired muscle regeneration after injury, with aberrant proliferation of satellite cells and delayed formation of new myofibers. These data reveal stage-specific roles of Brm during skeletal myogenesis, via formation of repressive and activatory SWI/SNF complexes.

Original languageEnglish
Pages (from-to)1037-1050
Number of pages14
JournalEMBO Reports
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

Keywords

  • Brahma
  • cyclin D1
  • skeletal myogenesis
  • SNF/SWI
  • transcription

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

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  • Cite this

    Albini, S., Coutinho Toto, P., Dall'Agnese, A., Malecova, B., Cenciarelli, C., Felsani, A., Caruso, M., Bultman, S. J., & Puri, P. L. (2015). Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis. EMBO Reports, 16(8), 1037-1050. https://doi.org/10.15252/embr.201540159