Sox9 represses gene expression via histone deacetylase activity

Sox9 is a transcription factor that is essential for chondrocyte development. Previously we have shown that p300, a ubiquitously expressed co-activator, interacted with Sox9 to activate gene expression. Even though both Sox9 and p300 are expressed in some other tissue, it is only chondrocyte that expresses type II collagen.

To clarify the mechanism that prevents Sox9 from activating chondrocyte-specific gene expression in those tissues, we examined the interaction between co-repressors and Sox9. Among the co-repressors, some HDACs interacted with Sox9 both in vitro and in vivo. Overexpression of those HDACs reduced the transcriptional activity of Gal4-fused Sox9. TSA, but not TPX-B, caused de-repression of transcription regulated by Sox9. These data identify Sox9 as the first transcription factor to interact with HDACs, and suggest that HDAC may bind to Sox9 to regulate tissue-specific gene expression.