Hairless Is a Nuclear Receptor Corepressor Essential for Skin Function

January 2009 in “ Nuclear Receptor Signaling ”

Catherine C. Thompson

Studysummary 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.

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

18 citations , October 2009 in “Endocrinology”

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.

Loss-Of-Function Mutations of an Inhibitory Upstream ORF in the Human Hairless Transcript Cause Marie Unna Hereditary Hypotrichosis

research Loss-Of-Function Mutations of an Inhibitory Upstream ORF in the Human Hairless Transcript Cause Marie Unna Hereditary Hypotrichosis

181 citations , January 2009 in “Nature Genetics”

In this study, researchers linked defects in U2HR, an inhibitory region in the HR gene, to Marie Unna hereditary hypotrichosis, suggesting a mechanism for controlling hair growth and addressing hair loss.

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 and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

74 citations , September 2006 in “Cell Cycle”

This review examines the role of Hairless, a nuclear receptor corepressor, in regulating Wnt signaling during hair cycling and reports no new clinical results.

research Roles of Jumonji and Jumonji Family Genes in Chromatin Regulation and Development

178 citations , May 2006 in “Developmental Dynamics”

This review discusses the role of jumonji family proteins in chromatin regulation and development, highlighting their involvement in transcriptional repression and histone demethylation, but reports no new experimental findings.

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 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 BMP Signaling in the Control of Skin Development and Hair Follicle Growth

165 citations , December 2004 in “Differentiation”

This review discusses the critical role of BMP signaling in the development and regulation of skin and hair follicles and notes that further research could aid therapeutic advances; it presents no new clinical results.

research Transient Activation of Beta-Catenin Signaling in Adult Mouse Epidermis Induces New Hair Follicles, Continuous Activation Maintains Tumors

335 citations , March 2004 in “Development”

This study found that continuous β-catenin signaling in adult mouse epidermis can reprogram hair follicles to form benign tumors, which regress after the signaling is discontinued.

research Identification of a Secreted BMP Antagonist, Ectodin, Integrating BMP, FGF, and SHH Signals from the Tooth Enamel Knot

243 citations , October 2003 in “Developmental biology”

This study identified ectodin as a novel BMP inhibitor that modulates BMP signaling in ectodermal development by interacting with SHH and FGF pathways.

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 Expression of ΔNLef1 in Mouse Epidermis Results in Differentiation of Hair Follicles into Squamous Epidermal Cysts and Formation of Skin Tumors

297 citations , January 2002 in “Development”

In this study, repressing β-catenin/Lef1 signalling in mouse epidermis led to progressive hair loss, dermal cysts, and spontaneous skin tumors with sebaceous differentiation, indicating altered keratinocyte differentiation and potential tumourigenic processes.

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 Tcf3 and Lef1 Regulate Lineage Differentiation of Multipotent Stem Cells in Skin

555 citations , July 2001 in “Genes & Development”

This study found that Tcf3 and Lef1 differently regulate cell differentiation in multipotent skin stem cells, with Tcf3 promoting follicle-like features and Lef1, when modified, promoting sebocyte differentiation.

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

137 citations , April 2001 in “Journal of Clinical Investigation”

This study found that alopecia in VDR-null mice persists despite undetectable vitamin D levels, indicating a defect in epithelial-mesenchymal communication due to the absence of ligand-independent receptor function.

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

303 citations , October 2000 in “Nature”

This study found that RXRα plays a critical role in hair cycling and keratinocyte functions in mice, likely through its interaction with VDR in epidermal cells.

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

47 citations , April 2000 in “Experimental Dermatology”

This study identified a novel missense mutation in the hairless gene in a Polish family, which may contribute to congenital atrichia with papular lesions by affecting the gene's function.

research Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

990 citations , October 1999 in “Development”

This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.

research The Hairless Gene of the Mouse: Relationship of Phenotypic Effects with Expression Profile and Genotype

52 citations , October 1999 in “Developmental Dynamics”

This study found that the hairless gene in mice has a more extensive role in development than previously thought, as indicated by its expression in various tissues and associated abnormalities in hr/hr mutants.

research The Role of the Hairless (Hr) Gene in the Regulation of Hair Follicle Catagen Transformation

166 citations , July 1999 in “American Journal Of Pathology”

This study found that the loss of a functional hr gene in mice leads to premature and abnormal hair follicle regression, disrupting normal hair cycling and architecture.

research Molecular and Functional Aspects of the Hairless (Hr) Gene in Laboratory Rodents and Humans

126 citations , October 1998 in “Experimental Dermatology”

This review provides an overview of the hairless gene in mice and humans, discussing its structure, expression, and implications for understanding skin physiology and human disorders related to gene disruption, but it reports no new empirical findings.

research Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

This study identified a missense mutation in the human hairless gene associated with a rare form of recessively inherited alopecia universalis, pinpointed on chromosome 8p12.

research The Secret Life of the Hair Follicle

745 citations , February 1992 in “Trends in genetics”

This article describes the potential role of various growth factors and molecules in regulating mammalian hair follicle development but does not present new experimental results.

research Dermal-Epidermal Interactions in Hair Follicle Development and Cycling

65 citations , October 1988 in “Clinics in dermatology”

This study found that dermal papilla cells may play a critical role in hair follicle development and cycling by promoting epidermal proliferation and potentially mediating systemic factors that influence follicle behavior.

research Catagen in the Hairless House Mouse

17 citations , November 1967 in “American Journal of Anatomy”

This study observed that the catagen phase in hairless mice displayed a slower shortening of the mutant epithelial column, resulting in longer total follicle length and abnormalities in the connective tissue sheath and glassy membrane.