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Al-Refaie, N. ; Padovani, F. ; Hornung, J. ; Pudelko, L ; Binando, F. ; Del Carmen Fabregat, A.* ; Zhao, Q.* ; Towbin, B.D.* ; Cenik, E.S.* ; Stroustrup, N.* ; Padeken, J.* ; Schmoller, K.M. ; Cabianca, D.S.

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

Nat. Cell Biol., DOI: 10.1038/s41556-024-01512-w (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Chromatin 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Map Kinase Cascade; Caenorhabditis-elegans; Starvation Responses; Genome Architecture; Nuclear Lamina; Polycomb Group; Rna-synthesis; Rag Gtpases; Transcription; Germline
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Zeitschrift Nature Cell Biology
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Functional Epigenetics (IFE)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-554900-001
G-554400-001
Förderungen European Research Council (ERC)
National Institutes of Health Office of Research Infrastructure Programs
Helmholtz Munich
German Research Foundation (Deutsche Forschungsgemeinschaft)
German Research Foundation (Deutsche Forschungsgemeinschaft) Schwerpunktprogramm 2202 Priority Programme 'Spatial Genome Architecture in Development and Disease'
National Institutes of Health
Welch Foundation
Human Frontier Science Program
Swiss National Science Foundation in the form of an Eccellenza Professorial Fellowship
European Research Council under the European Union
Spanish Ministry of Economy, Industry and Competitiveness to the European Molecular Biology Laboratory partnership
Centro de Excelencia Severo Ochoa
Centres de Recerca de Catalunya Programme/Generalitat de Catalunya
Spanish Ministry of Economy, Industry and Competitiveness Excelencia award
Swiss National Science Foundation (SNF)
Deutsche Forschungsgemeinschaft (German Research Foundation)
DOI 10.1038/s41556-024-01512-w
WOS ID 001315860000002
Scopus ID 85204420661
PubMed ID 39300311
Erfassungsdatum 2024-09-30
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