Trans-activation of the mouse cartilage-derived retinoic acid-sensitive protein gene by Sox9

The transcription factor Sox9 is capable of enhancing type If collagen gene expression and may play a crucial role in chondrogenesis, To determine whe ther Sox9 is an inducer of the chondrocyte phenotype, we investigated the r ole of Sox9 in transcription of another cartilage gene encoding the cartila ge-derived retinoic acid-sensitive protein (CD-RAP), CD-RAP is specifically expressed during chondrogenesis, We show here that Sox9 protein is able to bind to a SOX consensus sequence in the CD-RAP promoter. Mutation of the S OX moth led to decreased transcription of a CD-RAP promoter construct in ch ondrocytes, Overexpression of SOX9 resulted in a dose-dependent increased a ctivity of CD-RAP promoter-driven reporter gene in both chondrocytes and no nchondrogenic cells, A truncated SOX9, which contains a binding domain but no trans-activation function, inhibited CD-RAP promoter activity. Overexpre ssion of SOX9 increased the level of endogenous CD-RAP mRNA in chondrocytes , but was unable to induce endogenous gene expression in 10T1/2 mesenchymal cells or BALB/c-3T3 fibroblasts, These results suggest that Sox9 is a gene ral transcriptional regulator of cartilage-specific genes. However, Sox9 do es not appear to be able to induce the chondrocyte phenotype in nonchondrog enic cells, implying that other factors are involved in chondrogenesis.