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Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites
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. Usi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782443/ https://www.ncbi.nlm.nih.gov/pubmed/35061542 http://dx.doi.org/10.1126/sciadv.abj5688 |
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author | Mendoza, Mariel Egervari, Gabor Sidoli, Simone Donahue, Greg Alexander, Desi C. Sen, Payel Garcia, Benjamin A. Berger, Shelley L. |
author_facet | Mendoza, Mariel Egervari, Gabor Sidoli, Simone Donahue, Greg Alexander, Desi C. Sen, Payel Garcia, Benjamin A. Berger, Shelley L. |
author_sort | Mendoza, Mariel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8782443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87824432022-02-07 Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites Mendoza, Mariel Egervari, Gabor Sidoli, Simone Donahue, Greg Alexander, Desi C. Sen, Payel Garcia, Benjamin A. Berger, Shelley L. Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2022-01-21 /pmc/articles/PMC8782443/ /pubmed/35061542 http://dx.doi.org/10.1126/sciadv.abj5688 Text en 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). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Mendoza, Mariel Egervari, Gabor Sidoli, Simone Donahue, Greg Alexander, Desi C. Sen, Payel Garcia, Benjamin A. Berger, Shelley L. Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title | Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title_full | Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title_fullStr | Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title_full_unstemmed | Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title_short | Enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
title_sort | enzymatic transfer of acetate on histones from lysine reservoir sites to lysine activating sites |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782443/ https://www.ncbi.nlm.nih.gov/pubmed/35061542 http://dx.doi.org/10.1126/sciadv.abj5688 |
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