Regulation of Jumonji-domain containing histone demethylases by hypoxia inducible factor (HIF) 1-alpha

Patrick J Pollard (1) , Christoph Loenarz , David Mole , Michael A Mcdonough , Jonathan M Gleadle , Cj Schofield , Peter J Ratcliffe

1 Henry Wellcome Building for Molecular Physiology

The transcription factor hypoxia inducible factor (HIF) mediates a highly pleiotrophic response to hypoxia. Many recent studies have focused on defining the extent of this transcriptional response. Here we have analysed regulation by hypoxia amongst 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 Jumonji-domain containing histone demethylases as new classes of hypoxia regulated gene. Patterns of induction were consistent across a range of cell lines with JMJD1A and JMD2B demonstrating robust, and JMJD2C more modest, upregulation by hypoxia. Functional genetic and chromatin immunoprecipitation studies demonstrated the importance of HIF-1alpha 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.

Mots clés: Life Sciences

Patrick J Pollard, Christoph Loenarz, David Mole, Michael A Mcdonough, Jonathan M Gleadle, et al.. Regulation of Jumonji-domain containing histone demethylases by hypoxia inducible factor (HIF) 1-alpha. Biochemical Journal, 2008, 416 (3), pp.387-394. ⟨10.1042/BJ20081238⟩. ⟨hal-00479053⟩