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The regulation of myogenic progenitor cells during muscle regeneration is not clearly understood. We have previously shown that the Foxk1 gene, a member of the forkhead/winged helix family of transcription factors, is expressed in myogenic progenitor cells in adult skeletal muscle. In the present study, we utilize transgenic technology and demonstrate that the 4.6 kb upstream fragment of the Foxk1 gene directs β-galactosidase expression to the myogenic progenitor cell population. We further establish that Sox15 directs Foxk1 expression to the myogenic progenitor cell population, as it binds to an evolutionarily conserved site and recruits Fhl3 to transcriptionally coactivate Foxk1 gene expression. Knockdown of endogenous Sox15 results in perturbed cell cycle kinetics and decreased Foxk1 expression. Furthermore, Sox15 mutant mice display perturbed skeletal muscle regeneration, due in part to decreased numbers of satellite cells and decreased Foxk1 expression. These studies demonstrate that Sox15, Fhl3 and Foxk1 function to coordinately regulate the myogenic progenitor cell population and skeletal muscle regeneration. [ABSTRACT FROM AUTHOR]

We previously identified Xin, a novel actin binding protein, to be upregulated during the early phases of skeletal muscle regeneration. Here we demonstrate the transcriptional regulation of Xin within skeletal muscle and assess its function within satellite cell progeny (myoblasts). To define transcriptional regulation, promoter-reporter assays were performed in the presence of known myogenic transcription factors (MEF2, MyoD and Myf-5). All factors tested were capable of transactivating Xin promoter constructs, supporting the muscle-specific expression of Xin. To determine the function of Xin within myoblasts, we infected C2C12 myoblasts with adenoviral Xin shRNA and assessed proliferation, migration and differentiation. Inhibition of endogenous Xin expression resulted in a 26% increase in cell proliferation (581.4 ± 7.1 vs 461.8 ± 7.2 cells (x10³), counted 24h after initial 200,000 plated, n=5, p<0.05), a 20% increase in migratory capacity (288µm ± 6µm vs 240µm ± 3µm, distance traveled 24h after plate-scratch, n=3, p<0.05), and enhanced differentiation into mature myotubes as assessed by Western blot analysis of myosin heavy chain (0.488 ± 0.04 vs 0.159 ± 0.03 RLU, n=3, p<0.05). These findings are the first to demonstrate that alterations in Xin expression modify muscle precursor cell function. Future studies will elucidate the function of Xin within these cells during skeletal muscle regeneration. [ABSTRACT FROM AUTHOR]