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

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 intodistinct 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 isrequired for Ccnd1 repression and cell cycle arrest prior to the activationof muscle genes. Ccnd1 knockdown rescues the ability to exit the cell cycle in Brm-deficient myoblasts, but does not recoverterminal 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, via formation of repressive and activatory SWI/SNF complexes.