The transcription factor HIF (hypoxia-inducible factor) mediates a highly pleiotrophic response to hypoxia. Many recent studies have focused on defining the extent of this transcriptional response. In the present study we have analysed regulation by hypoxia among transcripts encoding human Fe(II)- and 2-oxoglutarate-dependent oxygenases. Our results show that many of these genes are regulated by hypoxia and define two groups of histone demethylases as new classes of hypoxia-regulated genes. Patterns of induction were consistent across a range of cell lines with JMJD1A (where JMJD is Jumonji-domain containing) and JMJD2B demonstrating robust, and JMJD2C more modest, up-regulation by hypoxia. Functional genetic and chromatin immunoprecipitation studies demonstrated the importance of HIF-1α in mediating these responses. Given the importance of histone methylation status in defining patterns of gene expression under different physiological and pathophysiological conditions, these findings predict a role for the HIF system in epigenetic regulation.
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Research Article|
November 26 2008
Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1α
Patrick J. Pollard;
Patrick J. Pollard
*Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K.
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Christoph Loenarz;
Christoph Loenarz
†Chemistry Research Laboratory and The Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
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David R. Mole;
David R. Mole
*Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K.
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Michael A. McDonough;
Michael A. McDonough
†Chemistry Research Laboratory and The Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
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Jonathan M. Gleadle;
Jonathan M. Gleadle
‡Department of Medicine, Flinders University and Flinders Medical Centre, Bedford Park, South Australia 5042, Australia
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Christopher J. Schofield;
Christopher J. Schofield
†Chemistry Research Laboratory and The Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
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Peter J. Ratcliffe
Peter J. Ratcliffe
1
*Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U.K.
1To whom correspondence should be addressed (email pjr@well.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 18 2008
Revision Received:
August 14 2008
Accepted:
August 19 2008
Accepted Manuscript online:
August 19 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 416 (3): 387–394.
Article history
Received:
June 18 2008
Revision Received:
August 14 2008
Accepted:
August 19 2008
Accepted Manuscript online:
August 19 2008
Citation
Patrick J. Pollard, Christoph Loenarz, David R. Mole, Michael A. McDonough, Jonathan M. Gleadle, Christopher J. Schofield, Peter J. Ratcliffe; Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1α. Biochem J 15 December 2008; 416 (3): 387–394. doi: https://doi.org/10.1042/BJ20081238
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