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

October 2009 in “ Endocrinology ”

Peter J. Malloy, Jining Wang, Kristin C. Jensen, David Feldman

Vitamin D receptor VDR Hairless HR isoforms human keratinocytes histone deacetylase 1 HDAC1 hair cycle regulation corepressor coactivator

Studysummary This study demonstrated that both HR isoforms are expressed in keratinocytes, but HRDelta1072-1126 lacks corepressor activity and may act as a coactivator by inhibiting HDAC recruitment to the VDR transcriptional complex.

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research Erasing the Methyl Mark: Histone Demethylases at the Center of Cellular Differentiation and Disease

667 citations , May 2008 in “Genes & Development”

This review discusses the biochemical and biological functions of histone demethylases and their potential involvement in human diseases, including cancer, but reports no new findings.

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

144 citations , December 2004 in “Molecular Endocrinology”

This study found that the effects of the vitamin D receptor on hair follicle cycling in mice are independent of its ability to bind a hormone, with specific domain mutations influencing hair regrowth outcomes.

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 Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

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.