Hairless is a histone H3K9 demethylase

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Liang LiuAngela M Christiano

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.

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Citations

Dec 15, 2015·Nature Reviews. Nephrology·Patrick H Maxwell, Kai-Uwe Eckardt
Dec 29, 2015·Journal of Medicinal Chemistry·Tom E McAllisterChristopher J Schofield
Dec 19, 2015·International Journal of Dermatology·Sabba MehmoodWasim Ahmad
Jan 28, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Sophie T WilliamsAkane Kawamura
Feb 24, 2016·The Journal of Investigative Dermatology·Nikolay V ZernovRena A Zinchenko
Jun 24, 2016·Nature Communications·Louise J WalportChristopher J Schofield
Mar 25, 2017·Chemical Reviews·H Ümit KaniskanJian Jin
May 26, 2017·Journal of Cellular Biochemistry·Anas MaatoughJui-Cheng Hsieh
Sep 8, 2018·Journal of Cellular Biochemistry·Lemlem BrookJui-Cheng Hsieh
Jun 30, 2016·Journal of Cellular Biochemistry·Lemlem BrookJui-Cheng Hsieh
Apr 23, 2021·Angewandte Chemie·Amelia BrasnettChristopher J Schofield
Sep 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ling LiuThomas A Rando

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