Al-Refaie, NadaPadovani, FrancescoHornung, JohannaPudelko, LorenzBinando, FrancescaCarmen Fabregat, Andrea delZhao, QiuxiaTowbin, Benjamin D.Sarinay Cenik, ElifStroustrup, NicholasPadeken, JanSchmoller, Kurt M.Cabianca, Daphne S.2024-12-022024-12-022024Al-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-w1465-7392http://hdl.handle.net/10230/68885Chromatin 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41556-024-01512-wChromatinNuclear organizationNucleolusNutrient signallingTranscriptioninfo:eu-repo/semantics/openAccess