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.

染色质结构是基因组功能的基本介质。禁食是整个动物王国的主要环境线索，但它如何影响三维 （3D） 基因组组织尚不清楚。在这里，我们表明禁食诱导秀丽隐杆线虫染色质的肠道特异性、可逆性和大规模空间重组。这种禁食诱导的 3D 基因组重组需要抑制营养感应 mTOR 通路，通过调节 RNA Pol I，而不是 Pol II 或 Pol III 起作用，并伴有核仁重塑。通过将 3D 基因组配置与动物的营养状况解耦，我们发现当染色质发生空间重组时，代谢和应激相关基因的表达增加，这表明 3D 基因组可能支持禁食动物的转录反应。我们的工作记录了由禁食触发的大规模染色质重组，并揭示了 mTOR 和 RNA Pol I 响应营养物质塑造基因组结构。