How do genes find their place in the nucleus, and what role does this location play in their activity? In a study published in PNAS, scientists have identified a new mechanism in Drosophila: certain proteins recognize the genes to be repressed and help anchor them to the periphery of the nucleus, an environment conducive to maintaining their repression.

Genes that change position depending on their activity

Transcription factors are proteins that control gene expression by binding to DNA. Although they are essential for the development and functioning of organisms, their mechanisms of action within the nucleus are still not fully understood. Specifically, their interaction with the three-dimensional organization of the genome is a key question.

In an article published in the journal PNAS, scientists examined Hox proteins, a family of transcription factors that has been highly conserved throughout evolution. They sought to understand how these proteins repress the expression of genes essential for autophagy—known as atg genes—in the fat body of the Drosophila larva, a tissue that plays a key role in storing and managing energy reserves.

This repression occurs during the larval “Feeding” stage, when the larva feeds and accumulates reserves. Later, the disappearance of Hox proteins allows for the expression of atg genes and the initiation of autophagy. This fundamental process enables cells to break down and recycle some of their own components. In Drosophila, it helps mobilize the reserves needed for metamorphosis and the first few days of the adult fly’s life.

Read more on the CNRS website

Reference

S. Vanderperre, L. Ajuria, M. Duffraisse, T. Da Silva, S. Vonau, J. Brocard, C. Forcet, and S. Merabet. “A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery”, Proc. Natl. Acad. Sci. U.S.A. 
DOI: https://doi.org/10.1073/pnas.2616645123