Fasting shapes chromatin architecture through an mTOR/RNA Pol I axis

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dc.contributor.authorAl-Refaie, Nada
dc.contributor.authorPadovani, Francesco
dc.contributor.authorHornung, Johanna
dc.contributor.authorPudelko, Lorenz
dc.contributor.authorBinando, Francesca
dc.contributor.authorCarmen Fabregat, Andrea del
dc.contributor.authorZhao, Qiuxia
dc.contributor.authorTowbin, Benjamin D.
dc.contributor.authorSarinay Cenik, Elif
dc.contributor.authorStroustrup, Nicholas
dc.contributor.authorPadeken, Jan
dc.contributor.authorSchmoller, Kurt M.
dc.contributor.authorCabianca, Daphne S.
dc.date.accessioned2024-12-02T16:19:08Z
dc.date.available2024-12-02T16:19:08Z
dc.date.issued2024
dc.description.abstractChromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom, yet how it impacts three-dimensional (3D) genome organization is unknown. Here we show that fasting induces an intestine-specific, reversible and large-scale spatial reorganization of chromatin in Caenorhabditis elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, acting through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodelling of the nucleolus. By uncoupling the 3D genome configuration from the animal's nutritional status, we find that the expression of metabolic and stress-related genes increases when the spatial reorganization of chromatin occurs, showing that the 3D genome might support the transcriptional response in fasted animals. Our work documents a large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.
dc.description.sponsorshipWe thank R. Schneider, M.-E. Torres-Padilla and S.M. Gasser for critical reading of the manuscript; the labs of H. Grosshans and F. Steiner; R. Gleason in X. Chen´s lab; the Caenorhabditis Genetics Center, funded by the National Institutes of Health Office of Research Infrastructure Programs (grant no. P40 OD010440CGC); and the C. elegans Gene Knockout Project at the Oklahoma Medical Research Foundation for sharing strains. We thank SunyBiotech for support in generating the rpc-1-mNeonGreen-AID allele. D.S.C. thanks Helmholtz Munich for support. Funding was provided by the German Research Foundation (Deutsche Forschungsgemeinschaft) Sonderforschungsbereiche (SFB) 1064, collaborative research center in chromatin dynamics (D.S.C.). The German Research Foundation (Deutsche Forschungsgemeinschaft) Schwerpunktprogramm 2202 Priority Programme ‘Spatial Genome Architecture in Development and Disease’ (D.S.C.). National Institutes of Health grant 5R35GM138340-03 (E.S.C.). The Welch Foundation F-2133-20230405 (E.S.C.). Human Frontier Science Program (career development award) (K.M.S.). The Swiss National Science Foundation in the form of an Eccellenza Professorial Fellowship (PCEFP3_181204) (B.D.T.). European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 852201) (N.S.). The Spanish Ministry of Economy, Industry and Competitiveness to the European Molecular Biology Laboratory partnership, the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), the Centres de Recerca de Catalunya Programme/Generalitat de Catalunya (N.S.). The Spanish Ministry of Economy, Industry and Competitiveness Excelencia award PID2020-115189GB-I00 (N.S.)
dc.format.mimetypeapplication/pdf
dc.identifier.citationAl-Refaie N, Padovani F, Hornung J, Pudelko L, Binando F, Del Carmen Fabregat A, et al. Fasting shapes chromatin architecture through an mTOR/RNA Pol I axis. Nat Cell Biol. 2024 Nov;26(11):1903-17. DOI: 10.1038/s41556-024-01512-w
dc.identifier.doihttp://dx.doi.org/10.1038/s41556-024-01512-w
dc.identifier.issn1465-7392
dc.identifier.urihttp://hdl.handle.net/10230/68885
dc.language.isoeng
dc.publisherNature Research
dc.relation.ispartofNat Cell Biol. 2024 Nov;26(11):1903-17
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/852201
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/2PE/PID2020-115189GB-I00
dc.rights© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.keywordChromatin
dc.subject.keywordNuclear organization
dc.subject.keywordNucleolus
dc.subject.keywordNutrient signalling
dc.subject.keywordTranscription
dc.titleFasting shapes chromatin architecture through an mTOR/RNA Pol I axis
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion

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