Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9.
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Tsuda M, Takahashi S, Takahashi Y, Asahara H
Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9.
J Biol Chem. 2003 Jul 18;278(29):27224-9. doi: 10.1074/jbc.M303471200. Epub 2003 May 5.
- PubMed ID
- 12732631 [ View in PubMed]
- Abstract
Chondrocytes are critical components for the precise patterning of a developing skeletal framework and articular joint formation. Sox9 is a key transcription factor that is essential for chondrocyte differentiation and chondrocyte-specific gene expressions; however, the precise transcriptional activation mechanism of Sox9 is not fully understood. Here we demonstrate that Sox9 utilizes a cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300 to exert its effects. Sox9 associates with CBP/p300 in the chondrosarcoma cell line SW1353 via its carboxyl termini activation domain in a cell type-specific manner. In promoter assays, CBP/p300 enhances Col2a1, which encodes cartilage-specific type II collagen gene promoter activity via Sox9. Chromatin immunoprecipitation shows that p300 is bound to the Col2a1 promoter region. Furthermore, the CBP/Sox9 complex disrupter peptide suppresses Col2a1 gene expression and chondrogenesis from mesenchymal stem cells. These data demonstrate that CBP and p300 function as co-activators of Sox9 for cartilage tissue-specific gene expression and chondrocyte differentiation.