Biology

Dr Samir Merabet
IGFL, UMR 5242 CNRS/ENS Lyon, France

Abstract:

Gene regulation is not occurring randomly within the nucleus, but is under
the control of nuclear matrix and chromatin-associated proteins that
participate to the genome-wide compartmentalization of transcriptionally
active and inactive regions. Surprisingly, how the specific regulatory
activity of transcription factors (TFs) could be influenced by the spatial
localization within the nucleus has rarely been considered. As a
consequence, whether and how nuclear matrix components could participate to
gene-specific regulatory complexes with TFs is not known.

Here we used Bimolecular Fluorescence Complementation (BiFC), Fluorescent
In Situ Hybridization (FISH) and super resolution microscopy to describe a
novel partnership involving Hox TFs and two proteins of the nuclear matrix
in the context of autophagy regulation in the *Drosophila* fat body: the
exportin Embargoed (Emb) and the LaminC (LamC). We found that the autophagy
repressive function of Hox proteins depends on their interaction with LamC,
which allows triggering autophagy related genes (*atg* genes) in a
repressive environment at the nuclear periphery. Later on, active nuclear
export of Hox proteins liberates *atg* loci for transcriptional activation,
leading to massive autophagy of the fat body and metamorphosis. This
clearance depends on the interaction with Emb through an atypical Hox
nuclear export motif that was previously known to regulate the interaction
of Hox proteins with other TFs. Our results demonstrate that
transcriptional specificity of Hox proteins is relying on the control of
their subnuclear localization through interactions with nuclear matrix
components.