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    Long-range gene regulation during vertebrate development and evolution



    Denis Duboule 

    Denis Duboule

    School of Life Sciences, Ecole Polytechnique Fédérale, Lausanne, Switzerland and
    Department of Genetics and Evolution, University of Geneva, Switzerland


    Jeudi 23 février 2017 à 12h00


     invité par Pascal Maire


    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    The emergence and evolution of digits was an essential step in the great success of land vertebrates. Hox genes members of the HoxD cluster are amongst the essential players in this developmental process and their mutations lead to severe limb phenotypes. During digital development, these genes are coordinately regulated, following the general principle of collinearity, which also applies to the regulation of these genes during the extension of the major body axis. We examined the transcriptional regulation of these genes and observed very long-range regulatory modalities. We further studied such regulations by chromosome conformation capture and chromatin signatures, using limb buds at both early and late stages combined with a large allelic series including targeted deletions, duplications and inversions. We show that different sets of active genes within the cluster can contact alternatively either the centromeric or the telomeric associated gene deserts, both matching Topologically Associating Domains (TADs). The global organization of this bimodal regulatory structure, as documented by 4C approaches, was also studied using DNA FISH on embryonic limb material and genetic analyses to try and disrupt it will be discussed. 

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