Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites

Mariel Mendoza, Gabor Egervari, Simone Sidoli, Greg Donahue, Desi C. Alexander, Payel Sen, Benjamin A. Garcia, Shelley L. Berger

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Histone acetylation is governed by nuclear acetyl-CoA pools generated, in part, from local acetate by metabolic enzyme acetyl-CoA synthetase 2 (ACSS2). We hypothesize that during gene activation, a local transfer of intact acetate occurs via sequential action of epigenetic and metabolic enzymes. Using stable isotope labeling, we detect transfer between histone acetylation sites both in vitro using purified mammalian enzymes and in vivo using quiescence exit in Saccharomyces cerevisiae as a change-of-state model. We show that Acs2, the yeast ortholog of ACSS2, is recruited to chromatin during quiescence exit and observe dynamic histone acetylation changes proximal to Acs2 peaks. We find that Acs2 is preferentially associated with the most up-regulated genes, suggesting that acetyl group transfer plays an important role in gene activation. Overall, our data reveal direct transfer of acetate between histone lysine residues to facilitate rapid transcriptional induction, an exchange that may be critical during changes in nutrient availability.

Original languageEnglish (US)
Article numbereabj5688
JournalScience Advances
Volume8
Issue number3
DOIs
StatePublished - Jan 2022
Externally publishedYes

ASJC Scopus subject areas

  • General

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