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

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

Published: 2022-01-21

DOI: 10.1126/sciadv.abj5688

Source: Full article


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