A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery
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.
Related
- RNA-guided transcriptional repression by TIGR-Tas systems
- Non-coding RNA 7SK drives tumor resistance by coupling local oncogenic activation with global transcriptional repression
- The m6A Reader IGF2BP2 Drives Depressive-like Behaviors Through m6A-Dependent Repression of Astrocytic GLUT1 and Glucose Metabolism
- Salidroside Represses the Viability of Mouse Sertoli Cell Line (TM4 Cells) via Repression of Ldha-Dependent Glycolysis
- AraC-like transcriptional activator CuxR binds c-di-GMP by a PilZ-like mechanism to regulate extracellular polysaccharide production.
BibTeX
@article{vanderperre2026hoxdependent,
title = {{A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery}},
author = {Solène Vanderperre and Leiore Ajuria and Marilyne Duffraisse and Tristan da Silva and Samantha Vonau and Jacques Brocard and Christelle Forcet and Samir Merabet},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = sep,
doi = {10.1073/pnas.2616645123},
url = {https://hal.science/hal-05745942v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Hox-dependent anchoring mechanism mediates transcriptional repression of autophagy-related genes at the nuclear periphery
AU - Solène Vanderperre
AU - Leiore Ajuria
AU - Marilyne Duffraisse
AU - Tristan da Silva
AU - Samantha Vonau
AU - Jacques Brocard
AU - Christelle Forcet
AU - Samir Merabet
PY - 2026
DA - 2026/09/01
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2616645123
UR - https://hal.science/hal-05745942v1
AB - 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.
SN - 0027-8424
SN - 1091-6490
ER -