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Elife. 2015 Apr 14;4. doi: 10.7554/eLife.06034.

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

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Institut de génomique fonctionnelle de Lyon, Centre National de Recherche Scientifique, Lyon, France.
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
Institut of Genetics, University of Mainz, Mainz, Germany.
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.


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.


BiFC; D. melanogaster; Hox; development; embryo; evolutionary biology; genomics; interactome; transcription factors

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