Modulation of Vitamin D Receptor Activity by the Corepressor Hairless: Differential Effects of Hairless Isoforms

The study explored the role of two Hairless (HR) isoforms in modulating Vitamin D receptor (VDR) activity, which is crucial in hair cycle regulation. Both HR isoforms were expressed in human keratinocytes, but they had different effects on VDR-mediated transactivation. The full-length HR isoform acted as a corepressor, interacting with histone deacetylase 1 (HDAC1) and repressing VDR activity, while the HRDelta1072-1126 isoform lacked corepressor activity, did not bind HDAC1, and even stimulated VDR activity. Mutations in specific glutamic acid residues eliminated HR's corepressor function. The findings suggested that HRDelta1072-1126 might act as a coactivator by preventing HDAC recruitment to the VDR complex, highlighting the differential roles of HR isoforms in hair biology.