• Galligan JJ, Rose KL, Beavers WN, Hill S, Tallman KA, Tansey WP, Marnett LJ. Stable histone adduction by 4-oxo-2-nonenal: a potential link between oxidative stress and epigenetics. Journal of the American Chemical Society. 2014 Aug 27;136(34). 11864-6. PMID: 25099620 [PubMed]. PMCID: PMC4151707.


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.