1. Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic progenitor cells.
- Author
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Meeson AP, Shi X, Alexander MS, Williams RS, Allen RE, Jiang N, Adham IM, Goetsch SC, Hammer RE, and Garry DJ
- Subjects
- Animals, Base Sequence, Binding Sites, Cell Cycle, Conserved Sequence, Embryo, Mammalian metabolism, Forkhead Transcription Factors genetics, Gene Expression Regulation, High Mobility Group Proteins chemistry, Intracellular Signaling Peptides and Proteins chemistry, Kinetics, LIM Domain Proteins, Mice, Mice, Knockout, Molecular Sequence Data, Muscle, Skeletal physiology, Mutagenesis, Promoter Regions, Genetic genetics, Protein Binding, Protein Structure, Tertiary, RNA, Messenger genetics, RNA, Messenger metabolism, Regeneration, SOX Transcription Factors, Stem Cells metabolism, Transcription Factors chemistry, Forkhead Transcription Factors metabolism, High Mobility Group Proteins metabolism, Intracellular Signaling Peptides and Proteins metabolism, Muscle, Skeletal cytology, Stem Cells cytology, Transcription Factors metabolism, Transcription, Genetic
- Abstract
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 beta-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.
- Published
- 2007
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