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.
de la Serna, I L; Roy, K; Carlson, K A et al. (2001) MyoD can induce cell cycle arrest but not muscle differentiation in the presence of dominant negative SWI/SNF chromatin remodeling enzymes. J Biol Chem 276:41486-91 |