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

April 2010 in “ Journal of Cellular Biochemistry ”

Jui Cheng Hsieh, Stephanie A. Slater, G. Kerr Whitfield, James L. Dawson, Grace Hsieh, Craig Sheedy, Carol A. Haussler, Mark R. Haussler

hairless corepressor vitamin D receptor VDR alopecia histone deacetylases chromatin remodeling transrepression protein-protein interfaces hydrophobic motifs histone demethylation hairless hair cycle

Studysummary This study concluded that the hairless protein interacts with the vitamin D receptor to repress transcription crucial for hair cycling, employing multiple protein interfaces and modulating chromatin structure. Our plain-language summary of this paper — not a Tressless recommendation.

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.

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