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

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• dc.contributor.author Princová, Jarmila
• dc.contributor.author Salat Canela, Clàudia, 1989-
• dc.contributor.author Daněk, Petr
• dc.contributor.author Marešová, Anna
• dc.contributor.author de Cubas, Laura
• dc.contributor.author Bähler, Jürg
• dc.contributor.author Ayté del Olmo, José
• dc.contributor.author Hidalgo Hernando, Elena
• dc.contributor.author Převorovský, Martin
• dc.date.accessioned 2023-01-25T07:32:43Z
• dc.date.available 2023-01-25T07:32:43Z
• dc.date.issued 2023
• dc.description.abstract 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.
• dc.description.sponsorship This work was supported by the Univerzita Karlova v Praze [grant number PRIMUS/MED/26 to M.P.], Grantová Agentura, Univerzita Karlova [grant number GA UK 1170217 to J.P.], Ministerio de Ciencia, Innovación y Universidades (Spain) [grant numbers PGC2018-093920-B-I00 to E.H. and PGC2018-097248-B-I00 to J.A.] and Unidad de Excelencia María de Maeztu (Spain) [grant number CEX2018-000792-M to E.H. and J.A.], and a Wellcome Trust Senior Investigator Award [grant number 095598/Z/11/Z] to J.B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Princová J, Salat-Canela C, Daněk P, Marešová A, de Cubas L, Bähler J, Ayté J, Hidalgo E, Převorovský M. Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress. PLoS Genet. 2023 Jan 10;19(1):e1010582. DOI: 10.1371/journal.pgen.1010582
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1010582
• dc.identifier.issn 1553-7390
• dc.identifier.uri http://hdl.handle.net/10230/55431
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Genet. 2023 Jan 10;19(1):e1010582
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-093920-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-097248-B-I00
• dc.rights © 2023 Princová et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Oxidative stress
• dc.subject.keyword Gene expression
• dc.subject.keyword Cellular stress responses
• dc.subject.keyword Schizosaccharomyces pombe
• dc.subject.keyword Gene regulation
• dc.subject.keyword Histones
• dc.subject.keyword Transcription factors
• dc.subject.keyword Chromatin
• dc.title Perturbed fatty-acid metabolism is linked to localized chromatin hyperacetylation, increased stress-response gene expression and resistance to oxidative stress
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion