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décembre 2021

  • Friday, 3 December 2021 11:30

    External Seminar

    Regulating gene expression in 3D during embryonic development

    Yad Gahvi-Helm

    IGFL, Lyon

    • C. Maurange
    • Embryonic development is controlled by the complex regulation of gene expression, which involves regulatory elements such as enhancers that can be located at various distances from their target gene. To regulate gene expression, distal enhancers need to be brought in close three-dimensional proximity to the promoter of their target gene, forming an enhancer-promoter chromatin loop. The 3D proximity between promoters and enhancers seems to be favored by the spatial configuration of chromatin into Topologically-Associating Domains (TADs). This led to the notion that TADs constitute basic functional domains driving enhancer-promoter interactions. However, our previous work indicates that chromosomal rearrangements affecting TAD boundaries only mildly affect gene expression (Ghavi-Helm et al. Nature Genetics 2019), questioning the actual function of TADs in regulating gene expression. Other factors besides genome topology have been suggested to promote the specific targeting of an enhancer to a given promoter, but the molecular mechanisms involved remain still largely unknown. To identify what might control enhancer-promoter interaction specificity, we systematically perturbed the endogenous twist locus (the master regulator of mesoderm formation) in Drosophila embryos. Thanks to this unique setup, we were able to analyze the functional impact of changes in the chromosomal location of an enhancer on viability, muscle formation, chromatin organization, and gene expression. The results are revealing surprising insights regarding the ability of enhancers to regulate gene expression across long distances.
  • Friday, 17 December 2021 11:30

    Internal Seminar