Mechanism of JmjC-Containing Protein Hairless in the Regulation of Vitamin D Receptor Function

September 2011 in “ Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ”

Yang, Mi, Ye Zhang, Yu-Fei Shen

Hairless protein vitamin D receptor VDR corepressor gene expression hair growth N-CoR transcriptional repression JmjC domain congenital alopecia hair follicle cycling HR

Studysummary Hairless protein helps control hair growth by regulating vitamin D receptor activity.

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The study examined the role of the Hairless (HR) protein in regulating the vitamin D receptor (VDR) function, focusing on its corepressor activity in gene expression related to hair growth. HR was found to repress VDR-mediated transactivation, with its interaction occurring in the nucleus alongside N-CoR, a transcriptional repression component. Mutations in the JmjC domain of HR impaired its corepressor function and altered its localization, leading to congenital alopecia. The study highlighted the importance of the JmjC domain and proper nuclear localization for HR's role in maintaining normal hair follicle cycling, using various cell lines and techniques to analyze these effects.

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research Hairless Is a Nuclear Receptor Corepressor Essential for Skin Function

30 citations , January 2009 in “Nuclear Receptor Signaling”

This study identified the Hairless (Hr) gene-encoded protein as a corepressor that plays a crucial role in maintaining skin and hair by regulating epithelial stem cell differentiation and gene expression via chromatin remodeling, which may impact both development and disease.

research Interactions of the Vitamin D Receptor with the Corepressor Hairless

42 citations , July 2007 in “Journal of Biological Chemistry”

This study found that most pathogenic HR mutants associated with atrichia with papular lesions had abolished corepressor activity due to defective interactions with histone deacetylases.

research Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

143 citations , May 2007 in “Proceedings of the National Academy of Sciences”

This study found that absence of the vitamin D receptor in keratinocytes impairs canonical Wnt signaling and leads to alopecia due to defects in keratinocyte stem cells.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

This study found that Hairless (Hr) acts as a corepressor of the vitamin D receptor (VDR) in human keratinocytes, blocking the action of vitamin D on keratinocyte differentiation.

research Hairless Triggers Reactivation of Hair Growth by Promoting Wnt Signaling

137 citations , September 2005 in “Proceedings of the National Academy of Sciences of the United States of America”

In this study, researchers found that transgenic expression of the Hairless gene in keratinocytes can restore hair follicle regeneration in Hr-deficient mice by repressing Wise, a modulator of Wnt signaling.

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

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

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

26 citations , October 2002 in “Journal of Investigative Dermatology”

This study identifies a mutation in the hairless gene that may impact thyroid receptor interaction, contributing to alopecia universalis congenita in an Arab Israeli patient.

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

178 citations , October 2001 in “Genes & Development”

This study found that the mammalian hairless gene encodes a corepressor protein that interacts with thyroid hormone receptors, providing insights into hair loss syndromes in humans and mice.

research Atrichia Caused by Mutations in the Vitamin D Receptor Gene Is a Phenocopy of Generalized Atrichia Caused by Mutations in the Hairless Gene

139 citations , September 2001 in “The journal of investigative dermatology/Journal of investigative dermatology”

This case report describes a patient with mutations in both alleles of the vitamin D receptor who exhibited hair loss clinically indistinguishable from generalized atrichia with papules, suggesting a potential genetic pathway shared with the hairless gene.