title: Lysine propionylation and butyrylation are novel post-translational modifications in histones.
abstract: The positively charged lysine residue plays an important role in protein folding and functions. Neutralization of the charge often has a profound impact on the substrate proteins. Accordingly all the known post-translational modifications at lysine have pivotal roles in cell physiology and pathology. Here we report the discovery of two novel, in vivo lysine modifications in histones, lysine propionylation and butyrylation. We confirmed, by in vitro labeling and peptide mapping by mass spectrometry, that two previously known acetyltransferases, p300 and CREB-binding protein, could catalyze lysine propionylation and lysine butyrylation in histones. Finally p300 and CREB-binding protein could carry out autopropionylation and autobutyrylation in vitro. Taken together, our results conclusively establish that lysine propionylation and lysine butyrylation are novel post-translational modifications. Given the unique roles of propionyl-CoA and butyryl-CoA in energy metabolism and the significant structural changes induced by the modifications, the two modifications are likely to have important but distinct functions in the regulation of biological processes.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Sprung
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Haydn
authors.initials: H
authors.lastname: Ball
authors.forename: Bhavani
authors.initials: B
authors.lastname: Sangras
authors.forename: Sung Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D006657:Histones; D010455:Peptides; D016159:Tumor Suppressor Protein p53; C024343:butyryl-coenzyme A; C009061:propionyl-coenzyme A; D050880:p300-CBP Transcription Factors; D008239:Lysine