Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

The study demonstrated that both the vitamin D receptor (VDR) and hairless (Hr) genes were crucial for the mammalian hair cycle, as mutations in either led to total alopecia. VDR functioned as a ligand-activated transcription factor, while Hr acted as a corepressor. The research showed that Hr significantly inhibited VDR-mediated transactivation, affecting both synthetic and natural VDR-responsive promoters. Hr was found to bind directly to VDR, suggesting an in vivo interaction, with the Hr contact site in VDR located in the ligand binding domain. Coimmunoprecipitation and functional studies indicated that VDR interacted with a C-terminal region of Hr. In situ hybridization in mouse skin showed colocalization of hr and VDR mRNAs in hair follicle cells, supporting the hypothesis of an intracellular interaction to repress VDR target gene expression.