title: Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.
abstract: We report the identification of a new type of histone mark, lysine 2-hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse histone Khib sites, including 27 unique lysine sites that are not known to be modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone mark was initially identified by MS and then validated by chemical and biochemical methods. Histone Khib shows distinct genomic distributions from histone Kac or histone Kcr during male germ cell differentiation. Using chromatin immunoprecipitation sequencing, gene expression analysis and immunodetection, we show that in male germ cells, H4K8hib is associated with active gene transcription in meiotic and post-meiotic cells. In addition, H4K8ac-associated genes are included in and constitute only a subfraction of H4K8hib-labeled genes. The histone Khib mark is conserved and widely distributed, has high stoichiometry and induces a large structural change. These findings suggest its critical role on the regulation of chromatin functions.
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Lunzhi
authors.initials: L
authors.lastname: Dai
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Peng
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Montellier
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California-San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ishii
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Debernardi
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Buchou
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.affiliation: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California-San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Fulai
authors.initials: F
authors.lastname: Jin
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Sabari
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California-San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Faculté de Médecine, La Tronche, France.
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.affiliation: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044127:Epigenesis, Genetic; D016678:Genome; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D006657:Histones; D006885:Hydroxybutyrates; C008039:2-hydroxyisobutyric acid; D008239:Lysine