論文 - 詳細
| RRC ID | 43802 |
|---|---|
| 著者 | Gu S, Boyer TG, Naski MC. |
| タイトル | Basic helix-loop-helix transcription factor Twist1 inhibits transactivator function of master chondrogenic regulator Sox9. |
| ジャーナル | J Biol Chem |
| Abstract |
Canonical Wnt signaling strongly inhibits chondrogenesis. Previously, we identified Twist1 as a critical downstream mediator of Wnt in repression of chondrocyte differentiation. However, the mechanistic basis for the antichondrogenic activity of Twist1 has not heretofore been established. Here, we show that Twist1 suppresses cartilage development by directly inhibiting the transcriptional activity of Sox9, the master regulator of chondrogenesis. Twist1, through its carboxyl-terminal Twist-box, binds to the Sox9 high mobility group DNA-binding domain, inhibiting Sox9 transactivation potential. In chondrocyte precursor cells, Twist1, in a Twist-box-dependent manner, inhibits Sox9-dependent activation of chondrocyte marker gene expression by blocking Sox9-enhancer DNA association. These findings identify Twist1 as an inhibitor of Sox9 and further suggest that the balance between Twist1 and Sox9 may determine the earliest steps of chondrogenesis. |
| 巻・号 | 287(25) |
| ページ | 21082-92 |
| 公開日 | 2012-6-15 |
| DOI | 10.1074/jbc.M111.328567 |
| PII | S0021-9258(20)49801-1 |
| PMID | 22532563 |
| PMC | PMC3375531 |
| MeSH | Animals Antigens, Differentiation / biosynthesis Antigens, Differentiation / genetics Cartilage / cytology Cartilage / metabolism Chondrogenesis / physiology* Enhancer Elements, Genetic / physiology Gene Expression Regulation / physiology HEK293 Cells HeLa Cells Humans Mice Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Binding Protein Structure, Tertiary SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism* Twist-Related Protein 1 / genetics Twist-Related Protein 1 / metabolism* Wnt Proteins / genetics Wnt Proteins / metabolism |
| IF | 4.238 |
| 引用数 | 23 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |