The transcriptional co-repressor TLE3 regulates myogenic differentiation by repressing the activity of the MyoD transcription factor

Shoichiro Kokabu, Chihiro Nakatomi, Takuma Matsubara, Yusuke Ono, William N. Addison, Jonathan W. Lowery, Mariko Urata, Aaron M. Hudnall, Suzuro Hitomi, Mitsushiro Nakatomi, Tsuyoshi Sato, Kenji Osawa, Tetsuya Yoda, Vicki Rosen, Eijiro Jimi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Satellite cells are skeletal muscle stem cells that provide myonuclei for postnatal muscle growth, maintenance, and repair/ regeneration in adults. Normally, satellite cells are mitotically quiescent, but they are activated in response to muscle injury, in which case they proliferate extensively and exhibit up-regulated expression of the transcription factor MyoD, a master regulator of myogenesis. MyoD forms a heterodimer with E proteins through their basic helix-loop-helix domain, binds to E boxes in the genome and thereby activates transcription at muscle-specific promoters. The central role of MyoD in muscle differentiation has increased interest in finding potential MyoD regulators. Here we identified transducin-like enhancer of split (TLE3), one of the Groucho/TLE family members, as a regulator of MyoD function during myogenesis. TLE3 was expressed in activated and proliferative satellite cells in which increased TLE3 levels suppressed myogenic differentiation, and, conversely, reduced TLE3 levels promoted myogenesis with a concomitant increase in proliferation. We found that, via its glutamine- and serine/proline-rich domains, TLE3 interferes with MyoD function by disrupting the association between the basic helix-loop-helix domain of MyoD and E proteins. Our findings indicate that TLE3 participates in skeletal muscle homeostasis by dampening satellite cell differentiation via repression of MyoD transcriptional activity.

Original languageEnglish
Pages (from-to)12885-12894
Number of pages10
JournalJournal of Biological Chemistry
Volume292
Issue number31
DOIs
Publication statusPublished - Aug 4 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kokabu, S., Nakatomi, C., Matsubara, T., Ono, Y., Addison, W. N., Lowery, J. W., Urata, M., Hudnall, A. M., Hitomi, S., Nakatomi, M., Sato, T., Osawa, K., Yoda, T., Rosen, V., & Jimi, E. (2017). The transcriptional co-repressor TLE3 regulates myogenic differentiation by repressing the activity of the MyoD transcription factor. Journal of Biological Chemistry, 292(31), 12885-12894. https://doi.org/10.1074/jbc.M116.774570