Proceedings of the National Academy of Sciences of the United States of AmericaSep 1, 2026

A Hox-controlled process keeps autophagy genes turned off near the cell nucleus

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Updated Sep 2, 2026

Abstract

The Hox protein Ultrabithorax (Ubx) represses autophagy-related genes by anchoring their locations to the nuclear periphery.

Ubx interacts with the nuclear lamina component Lamin-C to exert its repressive effects.
DNA-binding of Ubx is crucial for its physical interaction with Lamin-C and the repression of autophagy-related genes.
The spatial organization of target genes within a Lamin-C-rich nuclear compartment is essential for effective transcriptional repression.

Simplified

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.

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A Hox-controlled process keeps autophagy genes turned off near the cell nucleus

Abstract

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