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Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress

Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regula...

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Autores principales: Princová, Jarmila, Salat-Canela, Clàudia, Daněk, Petr, Marešová, Anna, de Cubas, Laura, Bähler, Jürg, Ayté, José, Hidalgo, Elena, Převorovský, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870116/
https://www.ncbi.nlm.nih.gov/pubmed/36626368
http://dx.doi.org/10.1371/journal.pgen.1010582
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author Princová, Jarmila
Salat-Canela, Clàudia
Daněk, Petr
Marešová, Anna
de Cubas, Laura
Bähler, Jürg
Ayté, José
Hidalgo, Elena
Převorovský, Martin
author_facet Princová, Jarmila
Salat-Canela, Clàudia
Daněk, Petr
Marešová, Anna
de Cubas, Laura
Bähler, Jürg
Ayté, José
Hidalgo, Elena
Převorovský, Martin
author_sort Princová, Jarmila
collection PubMed
description Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regulating transcription. Interestingly, it is becoming apparent that the metabolic state of the cell and certain metabolites can directly control the epigenetic information and gene expression. In the fission yeast Schizosaccharomyces pombe, the conserved Sty1 stress-activated protein kinase cascade is the main pathway responding to most types of stresses, and regulates the transcription of hundreds of genes via the Atf1 transcription factor. Here we report that fission yeast cells defective in fatty acid synthesis (cbf11, mga2 and ACC/cut6 mutants; FAS inhibition) show increased expression of a subset of stress-response genes. This altered gene expression depends on Sty1-Atf1, the Pap1 transcription factor, and the Gcn5 and Mst1 histone acetyltransferases, is associated with increased acetylation of histone H3 at lysine 9 in the corresponding gene promoters, and results in increased cellular resistance to oxidative stress. We propose that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis.
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spelling pubmed-98701162023-01-24 Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress Princová, Jarmila Salat-Canela, Clàudia Daněk, Petr Marešová, Anna de Cubas, Laura Bähler, Jürg Ayté, José Hidalgo, Elena Převorovský, Martin PLoS Genet Research Article Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regulating transcription. Interestingly, it is becoming apparent that the metabolic state of the cell and certain metabolites can directly control the epigenetic information and gene expression. In the fission yeast Schizosaccharomyces pombe, the conserved Sty1 stress-activated protein kinase cascade is the main pathway responding to most types of stresses, and regulates the transcription of hundreds of genes via the Atf1 transcription factor. Here we report that fission yeast cells defective in fatty acid synthesis (cbf11, mga2 and ACC/cut6 mutants; FAS inhibition) show increased expression of a subset of stress-response genes. This altered gene expression depends on Sty1-Atf1, the Pap1 transcription factor, and the Gcn5 and Mst1 histone acetyltransferases, is associated with increased acetylation of histone H3 at lysine 9 in the corresponding gene promoters, and results in increased cellular resistance to oxidative stress. We propose that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis. Public Library of Science 2023-01-10 /pmc/articles/PMC9870116/ /pubmed/36626368 http://dx.doi.org/10.1371/journal.pgen.1010582 Text en © 2023 Princová et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Princová, Jarmila
Salat-Canela, Clàudia
Daněk, Petr
Marešová, Anna
de Cubas, Laura
Bähler, Jürg
Ayté, José
Hidalgo, Elena
Převorovský, Martin
Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title_full Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title_fullStr Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title_full_unstemmed Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title_short Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
title_sort perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870116/
https://www.ncbi.nlm.nih.gov/pubmed/36626368
http://dx.doi.org/10.1371/journal.pgen.1010582
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