The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF

Posttranslational histone modifications serve to store epigenetic information and control both nucleosome assembly and recruitment of non-histone proteins. Histone methylation occurs on arginine and lysine residues and is involved in the regulation of gene transcription. A dynamic control of these m...

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Published inThe Journal of biological chemistry Vol. 283; no. 52; pp. 36542 - 36552
Main Authors Beyer, Sophie, Kristensen, Malene Maag, Jensen, Kim Steen, Johansen, Jens Vilstrup, Staller, Peter
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.12.2008
American Society for Biochemistry and Molecular Biology
Subjects
Arginine - chemistry
Base Sequence
Gene Expression Regulation
HeLa Cells
Histone Deacetylases - metabolism
Histones - chemistry
Humans
Hypoxia
Hypoxia-Inducible Factor 1 - metabolism
Jumonji Domain-Containing Histone Demethylases
Kidney - embryology
Lysine - chemistry
Microscopy, Fluorescence
Molecular Sequence Data
Oxidoreductases, N-Demethylating - physiology
Transcription Factors - physiology
Transcription, Chromatin, and Epigenetics
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Summary:Posttranslational histone modifications serve to store epigenetic information and control both nucleosome assembly and recruitment of non-histone proteins. Histone methylation occurs on arginine and lysine residues and is involved in the regulation of gene transcription. A dynamic control of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases. Here we show that the hypoxia-inducible factor HIF-1α binds to specific recognition sites in the genes encoding the jumonji family histone demethylases JMJD1A and JMJD2B and induces their expression. Accordingly, hypoxic cells express elevated levels of JMJD1A and JMJD2B mRNA and protein. Furthermore, we find increased expression of JMJD1A and JMJD2B in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of hypoxia-inducible factor. Studies on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program.
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This work was supported by the Biotech Research and Innovation Centre, the Danish Cancer Society, the Danish Cancer Research Foundation, Lykfeldts Legat, and the Novo Nordisk Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark. Tel.: 45-3532-5682; Fax: 45-3532-5669; E-mail: peter.staller@bric.ku.dk.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and Tables S2 and S2.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M804578200