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Chemical Labeling and Enrichment of Histone Glyoxal Adducts.

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

SUBMITTER: Ray DM

PROVIDER: S-EPMC9124041 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Chemical Labeling and Enrichment of Histone Glyoxal Adducts.

Ray Devin M DM Jennings Erin Q EQ Maksimovic Igor I Chai Xander X Galligan James J JJ David Yael Y Zheng Qingfei Q

ACS chemical biology 20220316 4

Because of their long half-lives and highly nucleophilic tails, histones are particularly susceptible to accumulating nonenzymatic covalent modifications, such as glycation. The resulting modifications can have profound effects on cellular physiology due to the regulatory role histones play in all DNA-templated processes; however, the complexity of Maillard chemistry on proteins makes tracking and enriching for glycated proteins a challenging task. Here, we characterize glyoxal (GO) modification ...[more]

PMID: 35294181

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