Stable histone adduction by 4-oxo-2-nonenal: a potential link between oxidative stress and epigenetics.

Galligan JJ, Rose KL, Beavers WN, Hill S, Tallman KA, Tansey WP, Marnett LJ
J Am Chem Soc. 2014 136 (34): 11864-6

PMID: 25099620 · PMCID: PMC4151707 · DOI:10.1021/ja503604t

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.

MeSH Terms (13)

Acylation Aldehydes Binding Sites Cell Line, Tumor DNA Adducts Epigenesis, Genetic Histones Humans Lysine Models, Molecular Nucleosomes Oxidative Stress Protein Processing, Post-Translational

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