title: Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo.
abstract: 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.
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Manon
authors: M
authors: Baëza
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Séverine
authors: S
authors: Viala
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Marjorie
authors: M
authors: Heim
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Amélie
authors: A
authors: Dard
authors: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
authors: Bruno
authors: B
authors: Hudry
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Marilyne
authors: M
authors: Duffraisse
authors: Institut of Genetics, University of Mainz, Mainz, Germany.
authors: Ana
authors: A
authors: Rogulja-Ortmann
authors: Technological Advances for Genomics and clinics, Institut national de la santé et de la recherche médicale, University Aix-Marseille, Parc Scientifique de Luminy, Marseille, France.
authors: Christine
authors: http://orcid.org/0000-0002-5563-6765
authors: C
authors: Brun
authors: Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
authors: Samir
authors: S
authors: Merabet
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019143:Evolution, Molecular; D005453:Fluorescence; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism*; D064267:Intrinsically Disordered Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000378:metabolism; D009928:Organ Specificity; D011485:Protein Binding; D060066:Protein Interaction Maps; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D064267:Intrinsically Disordered Proteins; D009842:Oligopeptides; D014157:Transcription Factors; D004247:DNA
keywords: BiFC; D. melanogaster; Hox; development; embryo; evolutionary biology; genomics; interactome; transcription factors