Analysis of Hairless Corepressor Mutants to Characterize Molecular Cooperation with the Vitamin D Receptor in Promoting the Mammalian Hair Cycle

The study analyzed the interaction between the hairless (Hr) corepressor and the vitamin D receptor (VDR) in the mammalian hair cycle. It was found that Hr interacts with VDR through multiple protein-protein interfaces, involving four hydrophobic motifs necessary for VDR transrepression. Mutations in Hr, corresponding to natural alopecia-causing mutations in mice and humans, were examined, revealing that certain mutations (C642G, G985W, N988S, D1030N, V1074M, H1143G, and V1154D) disrupted transrepressor activity while retaining VDR association. Additionally, Hr was shown to recruit histone deacetylases and potentially catalyze histone demethylation, contributing to chromatin remodeling and repression of VDR target genes that regulate the hair cycle.