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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Hairless is a histone H3K9 demethylase.

Authors: Liu, Liang; Kim, Hyunmi; Casta, Alex; Kobayashi, Yuki; Shapiro, Lawrence S; Christiano, Angela M

Published In FASEB J, (2014 Apr)

Abstract: The hairless (HR) protein contains a Jumonji C (JmjC) domain that is conserved among a family of proteins with histone demethylase (HDM) activity. To test whether HR possesses HDM activity, we performed a series of in vitro demethylation assays, which demonstrated that HR can demethylate monomethylated or dimethylated histone H3 lysine 9 (H3K9me1 or me2). Moreover, ectopic expression of wild-type HR, but not JmjC-mutant HR, led to pronounced demethylation of H3K9 in cultured human HeLa cells. We also show that two missense mutations in HR, which we and others described in patients with atrichia with papular lesions, abolished the demethylase activity of HR, demonstrating the role of HR demethylase activity in human disease. By ChIP-Seq analysis, we identified multiple new HR target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of HR. Our findings demonstrate for the first time that HR is a H3K9 demethylase that regulates epidermal homeostasis via direct control of its target genes.

PubMed ID: 24334705 Exiting the NIEHS site

MeSH Terms: Basic Helix-Loop-Helix Transcription Factors/genetics; Binding Sites/genetics; Blotting, Western; Caspase 14/genetics; Cells, Cultured; Chromatin Immunoprecipitation; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Histone Demethylases/chemistry; Histone Demethylases/genetics; Histone Demethylases/metabolism*; Histones/metabolism*; Humans; Jumonji Domain-Containing Histone Demethylases/chemistry; Jumonji Domain-Containing Histone Demethylases/genetics; Jumonji Domain-Containing Histone Demethylases/metabolism; Lysine/metabolism*; Methylation; Models, Molecular; Mutation; Promoter Regions, Genetic/genetics; Protein Structure, Tertiary; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism*; Tumor Suppressor Proteins/genetics

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