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

Area of Science:

• Cell Biology
• Genomics
• Developmental Biology

Background:

• Chromatin architecture is crucial for genome function.
• Fasting is a significant environmental factor, but its effect on 3D genome organization is not understood.

Purpose of the Study:

• To investigate the impact of fasting on three-dimensional (3D) genome organization.
• To identify the molecular mechanisms underlying fasting-induced chromatin changes.

Main Methods:

• Studied chromatin reorganization in Caenorhabditis elegans under fasting conditions.
• Investigated the roles of the mTOR pathway and RNA Polymerase I (Pol I) in this process.

Main Results:

• Fasting induces an intestine-specific, large-scale, and reversible reorganization of chromatin.
• This reorganization depends on the inhibition of the mTOR pathway and the regulation of RNA Pol I.
• Fasting-induced 3D genome changes are linked to increased expression of metabolic and stress-related genes.

Conclusions:

• Fasting profoundly alters genome architecture in a tissue-specific manner.
• The mTOR pathway and RNA Pol I are key regulators of nutrient-dependent 3D genome organization.
• 3D genome configuration plays a role in supporting the transcriptional adaptation to fasting.