TY - JOUR
T1 - Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites
AU - Mendoza, Mariel
AU - Egervari, Gabor
AU - Sidoli, Simone
AU - Donahue, Greg
AU - Alexander, Desi C.
AU - Sen, Payel
AU - Garcia, Benjamin A.
AU - Berger, Shelley L.
N1 - Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123285675&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abj5688
DO - 10.1126/sciadv.abj5688
M3 - Article
C2 - 35061542
AN - SCOPUS:85123285675
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 3
M1 - eabj5688
ER -