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

Patrick J Pollard, Christoph Loenarz, David R Mole, Michael A McDonough, Jonathan M Gleadle, Christopher J Schofield, Peter J Ratcliffe

Research output: Contribution to journalArticlepeer-review

Abstract

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-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.
Original languageEnglish
Pages (from-to)387-94
Number of pages8
JournalBiochemical Journal
Volume416
Issue number3
DOIs
Publication statusPublished - 15 Dec 2008

Keywords

  • Amino Acids, Dicarboxylic
  • Anoxia
  • Cell Line
  • Deferoxamine
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Jumonji Domain-Containing Histone Demethylases
  • Ketoglutaric Acids
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Oligonucleotide Array Sequence Analysis
  • Oxidoreductases, N-Demethylating
  • Oxygenases
  • Promoter Regions, Genetic
  • Protein Subunits
  • RNA, Small Interfering
  • Siderophores
  • Transcription Factors

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