The Transcriptional Co-Repressor TLE3 Regulates Myogenic Differentiation by Repressing the Activity of the MyoD Transcription Factor

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.

Creator

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

Publisher

• Copyright 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Language

• English

Identifier

• 10.1074/jbc.M116.774570

Parola chiave

• Co-Repressor TLE3
• myogenic differentiation
• MyoD transcription

Date created

• 8/4/2017

Related URL

• Final version of this article can be found at the following URL:  http://www.jbc.org/content/292/31/12885.long Marian University users can access the article here:  https://marianunivindianapolis.on.worldcat.org/oclc/7107052084

Resource type

• Article

Source

• The Journal of biological chemistry

Rights statement

• http://rightsstatements.org/vocab/InC/1.0/