title: Histone H3 globular domain acetylation identifies a new class of enhancers.
abstract: Histone acetylation is generally associated with active chromatin, but most studies have focused on the acetylation of histone tails. Various histone H3 and H4 tail acetylations mark the promoters of active genes. These modifications include acetylation of histone H3 at lysine 27 (H3K27ac), which blocks Polycomb-mediated trimethylation of H3K27 (H3K27me3). H3K27ac is also widely used to identify active enhancers, and the assumption has been that profiling H3K27ac is a comprehensive way of cataloguing the set of active enhancers in mammalian cell types. Here we show that acetylation of lysine residues in the globular domain of histone H3 (lysine 64 (H3K64ac) and lysine 122 (H3K122ac)) marks active gene promoters and also a subset of active enhancers. Moreover, we find a new class of active functional enhancers that is marked by H3K122ac but lacks H3K27ac. This work suggests that, to identify enhancers, a more comprehensive analysis of histone acetylation is required than has previously been considered.
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.|School of Biological Sciences, University of Essex, Colchester, UK.
authors.forename: Madapura M
authors.initials: MM
authors.lastname: Pradeepa
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Grimes
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
authors.forename: Yatendra
authors.initials: Y
authors.lastname: Kumar
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Olley
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
authors.forename: Gillian C A
authors.initials: GC
authors.lastname: Taylor
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France.|Helmholtz Zentrum München, Institute of Functional Epigenetics, Neuherberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D000107:Acetylation; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008239:Lysine / Q000378:metabolism
chemical_list: D006657:Histones; D008239:Lysine