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  • The EMBO Journal (2007) 26, 1902 - 1912
  • doi:10.1038/sj.emboj.7601635

Published online: 15 March 2007

Sox15 and Fhl3 transcriptionally coactivate Foxk1 and regulate myogenic progenitor cells

Annette P Meeson1,a, Xiaozhong Shi1,a, Matthew S Alexander1,a, R S Williams2, Ronald E Allen3, Nan Jiang1, Ibrahim M Adham4, Sean C Goetsch1, Robert E Hammer5 and Daniel J Garry1,6,7

  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
  2. Department of Medicine, Duke University Medical Center, Durham, NC, USA
  3. Department of Animal Sciences, University of Arizona, Tucson, AZ, USA
  4. Institute of Human Genetics, University of Göttingen, Göttingen, Germany
  5. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
  6. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
  7. Donald W Reynolds Cardiovascular Clinical Research Center at UT Southwestern Medical Center, Dallas, TX, USA

Correspondence to:

Daniel J Garry, Internal Medicine-Cardiology, NB11.118A, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8573, USA. Tel.: +1 214 648 1654; Fax: +1 214 648 1450; E-mail: daniel.garry@utsouthwestern.edu

aThese authors contributed equally to this work

Received 26 June 2006; Accepted 7 February 2007

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.

  • Keywords:

    • Foxk1,
    • muscle regeneration,
    • myogenic progenitors,
    • Sox15,
    • transgenic technologies