Regulation of developmental autophagy at the nuclear periphery

Hox proteins act as repressors of developmental autophagy in the Drosophila larval fat body. This repression occurs at the transcriptional level and is associated with the preferential positioning of autophagy-related (atg) genes at the nuclear periphery. Notably, this specific spatial localization depends on Hox proteins. Furthermore, Hox-mediated repression of autophagy relies on the nuclear lamina Lamin-C (LamC) protein. Both the Hox protein Ultrabithorax (Ubx) and LamC are preferentially enriched and preferentially interact in the atg-repressive nuclear compartment. Moreover, the Ubx DNA-binding domain is essential for Ubx-LamC interaction and to target atg loci to the nuclear periphery. Altogether, these findings uncover a novel molecular mechanism in which a Hox transcription factor acts as an anchoring molecule, bringing atg genes into a LamC-rich repressive nuclear microenvironment. Here, we describe this mechanism, adress the questions that remain to be explored and discuss its broader implications for other Hox/Lamin-dependent regulatory contexts.