title: Lysine succinylation and lysine malonylation in histones.
abstract: Histone protein post-translational modifications (PTMs) are significant for gene expression and DNA repair. Here we report the identification and validation of a new type of PTM in histones, lysine succinylation. The identified lysine succinylated histone peptides were verified by MS/MS of synthetic peptides, HPLC co-elution, and isotopic labeling. We identified 13, 7, 10, and 7 histone lysine succinylation sites in HeLa, mouse embryonic fibroblast, Drosophila S2, and Saccharomyces cerevisiae cells, respectively. We demonstrated that this histone PTM is present in all eukaryotic cells we examined. Mutagenesis of succinylation sites followed by functional assays implied that histone lysine succinylation can cause unique functional consequences. We also identified one and two histone lysine malonylation sites in HeLa and S. cerevisiae cells, respectively. Our results therefore increase potential combinatorial diversity of histone PTMs and suggest possible new connections between histone biology and metabolism.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Xie
authors.forename: Junbiao
authors.initials: J
authors.lastname: Dai
authors.forename: Lunzhi
authors.initials: L
authors.lastname: Dai
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Cheng
authors.forename: Yeming
authors.initials: Y
authors.lastname: Wu
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D004330:Drosophila; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008314:Malonates / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D006657:Histones; D008314:Malonates; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; D013386:Succinates; D008239:Lysine