Chemical Labeling and Enrichment of Histone Glyoxal Adducts br

Because of their long half-lives and highly nucleophilic tails, histones are particularly susceptible to accumulatingnonenzymatic covalent modifications, such as glycation. The resulting modifications can have profound effects on cellular physiologydue to the regulatory role histones play in all DNA-templated processes; however, the complexity of Maillard chemistry on proteinsmakes tracking and enriching for glycated proteins a challenging task. Here, we characterize glyoxal (GO) modifications on histonesusing quantitative proteomics and an aniline-derived GO-reactive probe. In addition, we leverage this chemistry to demonstrate thatthe glycation regulatory proteins DJ-1 and GLO1 reduce levels of histone GO adducts. Finally, we employ a two-round pull-downmethod to enrich histone H3 GO glycation and map these adducts to specific chromatin regions.