Stable Histone Adduction by 4‑Oxo-2-nonenal: A Potential Link between Oxidative Stress and Epigenetics

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.