title: Stable histone adduction by 4-oxo-2-nonenal: a potential link between oxidative stress and epigenetics.
abstract: Lipid electrophiles modify cellular targets, altering their function. Here, we describe histones as major targets for modification by 4-oxo-2-nonenal, resulting in a stable Lys modification structurally analogous to other histone Lys acylations. Seven adducts were identified in chromatin isolated from intact cells: four 4-ketoamides to Lys and three Michael adducts to His. A 4-ketoamide adduct residing at H3K27 was identified in stimulated macrophages. Modification of histones H3 and H4 prevented nucleosome assembly.
authors.affiliation: A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of †Biochemistry, ‡Chemistry, and §Pharmacology, ∥Mass Spectrometry Research Center, ⊥Center in Molecular Toxicology, and #Cell and Developmental Biology, Vanderbilt Institute of Chemical Biology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232-0146, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.forename: William N
authors.initials: WN
authors.lastname: Beavers
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.forename: Keri A
authors.initials: KA
authors.lastname: Tallman
authors.forename: William P
authors.initials: WP
authors.lastname: Tansey
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000215:Acylation; D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational
chemical_list: C403894:4-oxo-2-nonenal; D000447:Aldehydes; D018736:DNA Adducts; D006657:Histones; D009707:Nucleosomes; D008239:Lysine
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