ROLE OF CHROMATIN REMODELING IN MUSCLE DEVELOPMENT

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Chromatin is largely inaccessible to the transcriptional machinery. SWI/SNF is an evolutionarily conserved multiprotein complex that can modify chromatin structure in an ATP dependent manner and facilitate transcription factor binding in vitro. Although mammalian SWI/SNF subunits have been implicated in transcriptional control, cell division, differentiation and development, the genes regulated by mammalian SWI/SNF have not yet been identified in vivo. Preliminary evidence shows that mammalian SWI/SNF participates in myogenesis by activating transcription of two muscle specific genes, myogenin and myosin heavy chain. The specific aims of this proposal are to: 1) determine whether SWI/SNF is required for myogenin gene transcription due to its ability to alter chromatin structure and/or facilitate transcription factor binding. 2) determine whether SWI/SNF is needed for maintenance of muscle differentiation. 3) examine how SWI/SNF functions in the regulation of the muscle creatine kinase (MCK) enhancer. This work will characterize SWI/SNF function in vivo and increase our understanding of how alterations in chromatin structure serve to repress and derepress chromatin structure in both normal developmental processes and in cancer.