A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery.

Authors

Solène Vanderperre, Leiore Ajuria, Marilyne Duffraisse, Tristan Da Silva, Samantha Vonau, Jacques Brocard, Christelle Forcet, Samir Merabet

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 36. Pages e2616645123. Sep 08, 2026. Epub Sep 01, 2026.

Abstract

The spatial organization of the genome within the nucleus is critical for gene regulation, yet the mechanisms by which transcription factors (TFs) orchestrate this process remain poorly understood. Here, we demonstrate that the Drosophila Hox protein Ultrabithorax (Ubx) represses autophagy-related (atg) genes by tethering their loci to the nuclear periphery. This repressive activity relies on the interaction with the nuclear lamina component Lamin-C (LamC). Furthermore, we identify that DNA-binding of Ubx is determinant for both the physical interaction with nucleoplasmic LamC and the repression of atg genes in vivo. Together, our findings reveal a mechanism whereby a Hox TF functions as a spatial anchor, positioning target genes within a LamC-rich nuclear compartment to ensure efficient transcriptional repression.

PMID:
42679029
Bibliographic data and abstract were imported from PubMed on 02 Sep 2026.

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