Chromatin Succinylation Correlates with Active Gene Expression and Is Perturbed by Defective TCA Cycle Metabolism

John Smestad, Luke Erber, Yue Chen, L James Maher III

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Succinylation is a post-translational protein acylation modification that converts the cationic lysine side chain to an anion with large potential impacts on protein structure and function. Here we characterize the epigenome-wide distribution of succinyllysine marks in chromatin using chromatin immunoprecipitation sequencing (ChIP-seq). We estimate that more than one-third of all nucleosomes contain lysine succinylation marks and demonstrate a potential role of chromatin succinylation in modulating gene expression. We further demonstrate that defective tricarboxylic acid (TCA)cycle metabolism perturbs the succinyllysine distribution in chromatin, correlating with transcriptional responses. This is consistent with previous observations linking nucleosome succinylation with enhanced in vitro transcription. We additionally demonstrate that defective TCA cycle metabolism results in a DNA repair defect and sensitivity to genotoxic agents, consistent with previously reported chromatin hypersuccinylation effects observed in the context of SIRT7 depletion. Chromatin succinylation may thus represent a mechanism by which metabolism modulates both genome-wide transcription and DNA repair activities.

Original languageEnglish (US)
Pages (from-to)63-75
Number of pages13
JournalFood Science and Human Wellness
Volume2
DOIs
StatePublished - Apr 27 2018

Keywords

  • Cellular Physiology
  • Molecular Mechanism of Gene Regulation
  • Proteomics

ASJC Scopus subject areas

  • Food Science
  • General

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