Epigenetic regulation by histone demethylases in hypoxia

Epigenomics. 2015 Aug;7(5):791-811. doi: 10.2217/epi.15.24. Epub 2015 Apr 2.


The response to hypoxia is primarily mediated by the hypoxia-inducible transcription factor (HIF). Levels of HIF are regulated by the oxygen-sensing HIF hydroxylases, members of the 2-oxoglutarate (2OG) dependent oxygenase family. JmjC-domain containing histone lysine demethylases (JmjC-KDMs), also members of the 2OG oxygenase family, are key epigenetic regulators that modulate the methylation levels of histone tails. Kinetic studies of the JmjC-KDMs indicate they could also act in an oxygen-sensitive manner. This may have important implications for epigenetic regulation in hypoxia. In this review we examine evidence that the levels and activity of JmjC-KDMs are sensitive to oxygen availability, and consider how this may influence their roles in early development and hypoxic disease states including cancer and cardiovascular disease.

Keywords: 2-oxoglutarate dependent oxygenases; H3; HIF; KDMs; cancer; cardiovascular diseases; development; epigenetic regulation; histone 3; histone demethylases; hypoxia; oxygen kinetics; oxygen sensors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Epigenesis, Genetic*
  • Histones / metabolism*
  • Humans
  • Hypoxia / genetics*
  • Hypoxia / metabolism
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Lysine / metabolism
  • Methylation
  • Models, Genetic
  • Neoplasms / genetics
  • Neoplasms / metabolism


  • Histones
  • Jumonji Domain-Containing Histone Demethylases
  • Lysine