Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic progenitor cells

Annette P. Meeson, Xiaozhong Shi, Matthew S. Alexander, R. S. Williams, Ronald E. Allen, Nan Jiang, Ibrahim M. Adham, Sean C. Goetsch, Robert E Hammer, Daniel J. Garry

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1902-1912
Number of pages11
JournalEMBO Journal
Volume26
Issue number7
DOIs
StatePublished - Apr 4 2007

Keywords

  • Foxk1
  • Muscle regeneration
  • Myogenic progenitors
  • Sox15
  • Transgenic technologies

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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