title: Epigenetic regulation by histone demethylases in hypoxia.
abstract: 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.
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.|Radcliffe Department of Medicine, Division of Cardiovascular Medicine, BHF Centre of Research Excellence, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hancock
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.|Radcliffe Department of Medicine, Division of Cardiovascular Medicine, BHF Centre of Research Excellence, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Dunne
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Walport
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Flashman
authors.affiliation: Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, UK.|Radcliffe Department of Medicine, Division of Cardiovascular Medicine, BHF Centre of Research Excellence, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
authors.forename: Akane
authors.initials: A
authors.lastname: Kawamura
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine
keywords: 2-oxoglutarate dependent oxygenases; H3; HIF; KDMs; cancer; cardiovascular diseases; development; epigenetic regulation; histone 3; histone demethylases; hypoxia; oxygen kinetics; oxygen sensors