德国亥姆霍兹中心Daphne S. Cabianca团队近期取得重要工作进展。他们研究提出，禁食可以通过mTOR/RNA Pol I通路塑造染色质结构功能。相关研究成果2024年9月19日在线发表于《自然—细胞生物学》杂志上。

据介绍，染色质结构是基因组功能的基本媒介。禁食是整个动物王国的一个主要环境线索，但它如何影响三维（3D）基因组组织尚不清楚。

研究人员表明禁食可以诱导秀丽隐杆线虫肠道特异性、可逆性和大规模的染色质空间重组。这种禁食诱导的3D基因组重组需要抑制营养感应mTOR通路，该通路通过调节RNA Pol I而非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脱钩，研究人员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，表明3D基因组可能支持禁食动物的转录反应。

总之，这一研究工作记录了禁食引发的大规模染色质重组，并揭示了mTOR和RNA Pol I在营养物质的作用下能塑造基因组结构。

附：英文原文

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

Author: Al-Refaie, Nada, Padovani, Francesco, Hornung, Johanna, Pudelko, Lorenz, Binando, Francesca, del Carmen Fabregat, Andrea, Zhao, Qiuxia, Towbin, Benjamin D., Cenik, Elif Sarinay, Stroustrup, Nicholas, Padeken, Jan, Schmoller, Kurt M., Cabianca, Daphne S.

Issue&Volume: 2024-09-19

Abstract: 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.

DOI: 10.1038/s41556-024-01512-w

Source: https://www.nature.com/articles/s41556-024-01512-w