論文 - 詳細
| RRC ID | 50342 |
|---|---|
| 著者 | Kokabu S, Nakatomi C, Matsubara T, Ono Y, Addison WN, Lowery JW, Urata M, Hudnall AM, Hitomi S, Nakatomi M, Sato T, Osawa K, Yoda T, Rosen V, Jimi E. |
| タイトル | The transcriptional co-repressor TLE3 regulates myogenic differentiation by repressing the activity of the MyoD transcription factor. |
| ジャーナル | J Biol Chem |
| 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. |
| 巻・号 | 292(31) |
| ページ | 12885-12894 |
| 公開日 | 2017-8-4 |
| DOI | 10.1074/jbc.M116.774570 |
| PII | S0021-9258(20)40060-2 |
| PMID | 28607151 |
| PMC | PMC5546029 |
| MeSH | Activating Transcription Factor 3 / chemistry Activating Transcription Factor 3 / genetics Activating Transcription Factor 3 / metabolism Animals Cell Proliferation Cells, Cultured Co-Repressor Proteins / antagonists & inhibitors Co-Repressor Proteins / chemistry Co-Repressor Proteins / genetics Co-Repressor Proteins / metabolism* Gene Deletion Gene Expression Regulation, Developmental* Helix-Loop-Helix Motifs Male Mice Mice, Inbred C57BL Muscle Development* Muscle Fibers, Skeletal / cytology Muscle Fibers, Skeletal / metabolism* MyoD Protein / antagonists & inhibitors* MyoD Protein / chemistry MyoD Protein / genetics MyoD Protein / metabolism Myoblasts / cytology Myoblasts / metabolism* Peptide Fragments / antagonists & inhibitors Peptide Fragments / chemistry Peptide Fragments / genetics Peptide Fragments / metabolism Protein Interaction Domains and Motifs Protein Multimerization RNA Interference Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / metabolism Recombinant Proteins / chemistry Recombinant Proteins / metabolism Satellite Cells, Skeletal Muscle / cytology Satellite Cells, Skeletal Muscle / metabolism* |
| IF | 4.238 |
| 引用数 | 10 |
| リソース情報 | |
| 遺伝子材料 | pcDEF3-Myc-mTLE3 (RDB15784) pGL4.26_0.8kb-Luc (RDB15785) pcDEF3_Myc_mMef2 (RDB15786) pcDEF3_Myc-mMyoD (RDB15787) pcDNA3.1_mTLE3-V5-His (RDB15788). |