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

TLDR Certain mutations in the hairless protein disrupt its ability to regulate the 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.

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

Research cited in this study

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

research Quantification of the Vitamin D Receptor-Coregulator Interaction

research The 'Bald Mill Hill' Mutation in the Mouse Is Associated with an Abnormal, Mislocalized HR BMH Protein

research Interactions of the Vitamin D Receptor with the Corepressor Hairless

research A Novel Missense Mutation in the Mouse Hairless Gene Causes Irreversible Hair Loss: Genetic and Molecular Analyses of Hrm1Enu

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

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

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research A Novel Missense Mutation Affecting the Human Hairless Thyroid Receptor Interacting Domain 2 Causes Congenital Atrichia

research Clinical and Molecular Diagnostic Criteria of Congenital Atrichia with Papular Lesions

research The Hairless Gene in Androgenetic Alopecia: Results of a Systematic Mutation Screening and a Family-Based Association Approach

research The Hairless Gene Mutated in Congenital Hair Loss Disorders Encodes a Novel Nuclear Receptor Corepressor

research Metabolic And Cellular Analysis Of Alopecia In Vitamin D Receptor Knockout Mice

research Skin Abnormalities Generated by Temporally Controlled RXRα Mutations in Mouse Epidermis

research A Novel Missense Mutation (C622G) in the Zinc-Finger Domain of the Human Hairless Gene Associated with Congenital Atrichia with Papular Lesions

research Novel Hairless Mutations in Two Kindreds with Autosomal Recessive Papular Atrichia

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