SRA

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 an intestine-specific, 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, through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodeling of the nucleolus. By uncoupling the 3D genome configuration from the animal´s nutritional status we find that the spatial reorganization of chromatin correlates with the expression of metabolic and stress-related genes, potentially supporting the transcriptional response in 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. Overall design: RNA was extracted from intestines dissected from day 1 adults in TIR1 and in TIR1 with RPOA-2-AID worms exposed to auxin. Briefly, synchronized L1s by hypochlorite treatment were grown on OP50-seeded NGM plates for 72 hours until day 1 of adulthood. Next, they were picked from the plates and transferred onto auxin plates seeded with OP50 and maintained for the indicated time. Three time points were analyzed 0h, 12h and 24h on auxin. DCW143 (ieSi57 [eft-3p::TIR1::mRuby::unc-54 3'UTR+Cbr-unc-119(+)] II) outcrossed 1x), DCW180 (qzIs15[rpoa-2p::degron1(TIR1)::GFP::rpoa-2] I; ieSi57 [eft-3p::TIR1::mRuby::unc-54 3'UTR+Cbr-unc-119(+)] outcrossed 1x), DCW448 (ieSi57 [eft-3p::TIR1::mRuby::unc-54 3'UTR+Cbr-unc-119(+)] II) outcrossed 3x), DCW447 (qzIs15[rpoa-2p::degron1(TIR1)::GFP::rpoa-2] I; ieSi57 [eft-3p::TIR1::mRuby::unc-54 3'UTR+Cbr-unc-119(+)] outcrossed 3x).