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[Preprint]. 2023 Jul 22:2023.07.22.550032. [Version 1] doi: 10.1101/2023.07.22.550032

An mTOR/RNA pol I axis shapes chromatin architecture in response to fasting

Nada Al-Refaie, Francesco Padovani, Francesca Binando, Johanna Hornung, Qiuxia Zhao, Benjamin D Towbin, Elif Sarinay Cenik, Nicholas Stroustrup, Kurt M Schmoller, Daphne S Cabianca
PMCID: PMC10370172  PMID: 37503059

Abstract

Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown. Here, we show that fasting induces a reversible and large-scale spatial reorganization of chromatin in C. elegans . This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, a major regulator of ribosome biogenesis. Remarkably, loss of transcription by RNA Pol I, but not RNA Pol II nor Pol III, induces a similar 3D genome reorganization in fed animals, and prevents the restoration of the fed-state architecture upon restoring nutrients to fasted animals.

Our work documents the first 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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