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MSRC Proteomics Core Laboratory

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

AUTHORS

Galligan JJJames 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.

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.

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