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


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.

SUBMITTER: Galligan JJ 

PROVIDER: S-EPMC4151707 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Galligan James J JJ   Rose Kristie L KL   Beavers William N WN   Hill Salisha S   Tallman Keri A KA   Tansey William P WP   Marnett Lawrence J LJ  

Journal of the American Chemical Society 20140811 34


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 prevente  ...[more]

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