Synergistic Effect of SRY and Its Direct Target, WDR5, on Sox9 Expression

摘要: SRY is a sex-determining gene that encodes transcription factor, which triggers male development in most mammals. The molecular mechanism of action testis determination is, however, poorly understood. In this study, we demonstrate WDR5, WD-40 repeat protein, direct target SRY. EMSA experiments and ChIP assays showed could bind to the WDR5 promoter directly. Overexpression LNCaP cells significantly increased expression concurrent with histone H3K4 methylation on promoter. To specifically address whether contributes regulation, introduced 4-hydroxy-tamoxifen-inducible allele into cells. Conditional triggered enrichment resulting induction transcription. We found was self regulating through positive feedback loop. interacted were colocalized addition, interaction resulted activation Sox9 while repressing β-catenin. These results suggest that, conjunction SRY, plays an important role sex determination.