Transcriptional co-activator CBP/p300 regulates chondrocyte-specific gene expression via association with Sox9

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 CBP/p300 to exert its effects. Sox9 associates with CBP/p300 in chondrocyte 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, the 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 CBP/p300 functions as a coactivator of Sox9 for cartilage tissue-specific gene expression and chondrocyte differentiation.