CHARACTERIZING THE ROLE OF THE TRANSCRIPTION FACTORS, αNAC, BTF3 AND SKNAC, IN MYOGENESIS

Myogenesis is a complex and tightly regulated process, the end result of which is the formation of multinucleated myofibers. Muscle formation requires the precise expression of multiple myogenic regulatory factors (MRFs), whose expression regulates transcription of muscle specific proteins. Alteration in the expression of a muscle specific gene or protein ultimately results in muscle dysfunction. The inappropriate expression of factors that control muscle development may also be a contributing factor in Rhabdomyosarcoma, a pediatric cancer that accounts for most soft tissue sarcomas that arise in children. Previous studies suggest that the regulation of αNAC, BTF3, and skNAC are vital for normal myogenesis. Alterations in these factors results in retarded development and severe disorganization of muscle tissue. We hypothesized that αNAC, BTF3, and skNAC are imperative transcription factors whose dysregulation significantly alters the kinetics of C2C12 cell (murine skeletal muscle cells) myogenesis. We have shown that erroneous expression of these transcription factors is detrimental to myogenesis. In addition, we have shown that these transcription factors are recruited to muscle specific gene promoters during the myogenic differentiation program and the expression of αNAC, BTF3, and skNAC may potentiate the expression of the MRFs. Together, our experiments suggest that the expression of αNAC, BTF3, and skNAC are essential for the normal progression of myogenesis