Hox proteins display a common and ancestral ability to diversify their interaction mode with the PBC class cofactors
| Autor: | Marie-Claire Delfini, Samir Merabet, Bruno Hudry, Yacine Graba, Sophie Remacle, René Rezsohazy |
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| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unit of Developmental Genetics, Université Catholique de Louvain = Catholic University of Louvain (UCL), Unit of Veterinary Sciences, Institut des Sciences de la Vie, UCL - SST/ISV - Institut des sciences de la vie, CONTENSIN, Magali |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Embryo
Nonmammalian Chick Embryo Bioinformatics Mice Bimolecular fluorescence complementation Chlorocebus aethiops MESH: Gene Expression Regulation Developmental Drosophila Proteins MESH: Animals Biology (General) Hox gene skin and connective tissue diseases MESH: Evolution Molecular Genetics 0303 health sciences General Neuroscience 030302 biochemistry & molecular biology Gene Expression Regulation Developmental [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis MESH: Chick Embryo MESH: COS Cells Drosophila melanogaster COS Cells embryonic structures Synopsis General Agricultural and Biological Sciences Drosophila Protein Research Article animal structures QH301-705.5 MESH: Drosophila Proteins Computational biology Biology DNA-binding protein digestive system General Biochemistry Genetics and Molecular Biology Protein–protein interaction MESH: Drosophila melanogaster Evolution Molecular 03 medical and health sciences MESH: Homeodomain Proteins Animals Transcription factor MESH: Mice 030304 developmental biology Homeodomain Proteins General Immunology and Microbiology MESH: Embryo Nonmammalian biology.organism_classification MESH: Cercopithecus aethiops digestive system diseases [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis Homeobox |
| Zdroj: | PLoS Biology PLoS Biology, Public Library of Science, 2012, 10 (6), pp.e1001351. ⟨10.1371/journal.pbio.1001351⟩ PLoS Biology, Vol. 10, no.6, p. 1-17 (2012) PLoS Biology, Vol 10, Iss 6, p e1001349 (2012) PLoS Biology, 2012, 10 (6), pp.e1001351. ⟨10.1371/journal.pbio.1001351⟩ PLoS Biology, Vol 10, Iss 6, p e1001351 (2012) |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.1001351⟩ |
| Popis: | Hox protein function during development and evolution relies on conserved multiple interaction modes with cofactors of the PBC and Meis families. Hox transcription factors control a number of developmental processes with the help of the PBC class proteins. In vitro analyses have established that the formation of Hox/PBC complexes relies on a short conserved Hox protein motif called the hexapeptide (HX). This paradigm is at the basis of the vast majority of experimental approaches dedicated to the study of Hox protein function. Here we questioned the unique and general use of the HX for PBC recruitment by using the Bimolecular Fluorescence Complementation (BiFC) assay. This method allows analyzing Hox-PBC interactions in vivo and at a genome-wide scale. We found that the HX is dispensable for PBC recruitment in the majority of investigated Drosophila and mouse Hox proteins. We showed that HX-independent interaction modes are uncovered by the presence of Meis class cofactors, a property which was also observed with Hox proteins of the cnidarian sea anemone Nematostella vectensis. Finally, we revealed that paralog-specific motifs convey major PBC-recruiting functions in Drosophila Hox proteins. Altogether, our results highlight that flexibility in Hox-PBC interactions is an ancestral and evolutionary conserved character, which has strong implications for the understanding of Hox protein functions during normal development and pathologic processes. Author Summary Hox proteins are key transcriptional regulators of animal development, famously helping to determine identity along the anterior-posterior body axis. Although their evolution and developmental roles are well established, the molecular mechanisms underlying their specific functions remain poorly characterized. The current dominant view is that interaction with different members of the PBC family of transcription factors confers specific DNA-binding properties on different Hox proteins. However, this idea conflicts with in vitro evidence that a short “hexapeptide” (HX) motif shared by most Hox proteins is solely responsible for generic PBC recruitment. Here we have used the BiFC (bimolecular fluorescence complementation) method to address the global importance of the HX motif for Hox-PBC interactions in living cells and living animals including fruit flies and chick embryos. We observe that most interactions between Hox and PBC proteins do not depend on HX, and that alternative protein motifs are widely used for PBC recruitment in vivo. We also show that DNA binding by a second family of cofactors, the Meis proteins, unmasks these alternative interaction modes and that this property is conserved not only across Bilateria, but also in the basal animal phylum Cnidaria. Taken together, our results demonstrate that Hox-PBC partnership relies on multiple interaction modes, which can be influenced by additional transcriptional partners. We propose that this ancestral feature has been essential for ensuring Hox functional plasticity during development and evolution. |
| Databáze: | OpenAIRE |
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