Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic progenitor cells

EMBO J. 2007 Apr 4;26(7):1902-12. doi: 10.1038/sj.emboj.7601635. Epub 2007 Mar 15.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Cycle
  • Conserved Sequence
  • Embryo, Mammalian / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation
  • High Mobility Group Proteins / chemistry
  • High Mobility Group Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kinetics
  • LIM Domain Proteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Muscle, Skeletal / cytology*
  • 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 / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Fhl3 protein, mouse
  • Forkhead Transcription Factors
  • Foxk1 protein, mouse
  • High Mobility Group Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • RNA, Messenger
  • SOX Transcription Factors
  • Sox15 protein, mouse
  • Transcription Factors