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

Authors

Galligan JJ James J , Rose KL Kristie L , Beavers WN William N , Hill S Salisha , Tallman KA Keri A , Tansey WP William P , Marnett LJ Lawrence J .
Journal of the American Chemical Society. 2014 8 27; 136(34).
11864-6

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.