title: Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase.
abstract: Histone N(ϵ)-methyl lysine demethylases are important in epigenetic regulation. KDM4E (histone lysine demethylase 4E) is a representative member of the large Fe(II)/2-oxoglutarate- dependent family of human histone demethylases. In the present study we report kinetic studies on the reaction of KDM4E with O2. Steady-state assays showed that KDM4E has a graded response to O2 over a physiologically relevant range of O2 concentrations. Pre-steady state assays implied that KDM4E reacts slowly with O2 and that there are variations in the reaction kinetics which are dependent on the methylation status of the substrate. The results demonstrate the potential for histone demethylase activity to be regulated by oxygen availability.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Sánchez-Fernández
authors.forename: Hanna
authors.initials: H
authors.lastname: Tarhonskaya
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Qahtani
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hopkinson
authors.forename: James S O
authors.initials: JS
authors.lastname: McCullagh
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: Emily
authors.initials: E
authors.lastname: Flashman
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D015394:Molecular Structure; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D013053:Spectrophotometry; D013379:Substrate Specificity; D013386:Succinates / Q000737:chemistry / Q000378:metabolism
chemical_list: D006657:Histones; D007656:Ketoglutaric Acids; D010455:Peptides; D013386:Succinates; D007501:Iron; D056484:Jumonji Domain-Containing Histone Demethylases; C549811:KDM4E protein, human; D008239:Lysine; D010100:Oxygen