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Hairless is a histone H3K9 demethylase
Author(s) -
Liu Liang,
Kim Hyunmi,
Casta Alex,
Kobayashi Yuki,
Shapiro Lawrence S.,
Christiano Angela M.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-237677
Subject(s) - demethylase , histone , demethylation , transactivation , hairless , histone h3 , mutant , biology , microbiology and biotechnology , histone methylation , chemistry , gene , genetics , gene expression , dna methylation
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 mono‐methylated or dimethylated histone H3 lysine 9 (H3K9mel 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 ChlP‐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.—Liu, L., Kim, H., Casta, A., Kobayashi, Y., Shapiro, L. S., Christiano, A. M. Hairless is a histone H3K9 demethylase. FASEB J. 28, 1534–1542 (2014). www.fasebj.org