Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

Manon Baëza (1) , Séverine Viala (1) , Marjorie Heim (1) , Amélie Dard (1) , Bruno Hudry (2) , Marilyne Duffraisse (1) , Ana Rogulja-Ortmann (3) , Christine Brun (4, 5) , Samir Merabet (1)

1 IGFL - Institut de Génomique Fonctionnelle de Lyon
2 Imperial College London
3 Institut of Genetics
4 CNRS - Centre National de la Recherche Scientifique
5 TAGC - Technologies avancées pour le génôme et la clinique

Hox proteins are well-established developmental regulators that coordinate cell fate and morphogenesis throughout embryogenesis. In contrast, our knowledge of their specific molecular modes of action is limited to the interaction with few cofactors. Here, we show that Hox proteins are able to interact with a wide range of transcription factors in the live Drosophila embryo. In this context, specificity relies on a versatile usage of conserved short linear motifs (SLiMs), which, surprisingly, often restrains the interaction potential of Hox proteins. This novel buffering activity of SLiMs was observed in different tissues and found in Hox proteins from cnidarian to mouse species. Although these interactions remain to be analysed in the context of endogenous Hox regulatory activities, our observations challenge the traditional role assigned to SLiMs and provide an alternative concept to explain how Hox interactome specificity could be achieved during the embryonic development.

Mots clés: BIMOLECULAR FLUORESCENCE COMPLEMENTATION; PROTEIN INTERACTIONS; TRANSCRIPTION FACTORS; TARGET GENE; DROSOPHILA-MELANOGASTER; INTERACTION MODULES; CELL REGULATION; ABDOMINAL-A; REPRESSION; REGIONS

Domaines: Biologie cellulaire; Biochimie, Biologie Moléculaire

Manon Baëza, Séverine Viala, Marjorie Heim, Amélie Dard, Bruno Hudry, et al.. Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo. eLife, 2015, 4 (UNSP e06034), ⟨10.7554/eLife.06034⟩. ⟨hal-01215867⟩