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    HIV-1 integration sites in the context of 3D genome structure and function: Impact on viral and host gene expression

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    Séminaire de l'Institut Cochin

    Jeudi 30 janvier 2020 - 12h00 - Salle de conférence Rosalind Franklin, 2ème étage

     


    Monsef Benkirane

    Institut de Génétique Humaine CNRS, Université de Montpellier, France

     

     invité par Stéphane Emiliani

    Institut Cochin, 22 rue Méchain, 75014 Paris

     

    Résumé

    HIV integration into the host genome is essential to ensure productive infection and viral persistence in the infected cells. Understanding retrovirus-host interactions at the genomic level will reveal features of both viral and host genome dictating integration sites selection and the impact of proviruses on host genome function. By integrating host epigenomic, transcriptomic data and 3D genomic structure of primary CD4 T cell, we identified key chromatin and structural features associated with HIV integration sites. Promoter capture HiC data revealed that HIV-1 target highly connected fragments within the genome and that integration sites are highly enriched in specific gene communities that we name Recurrent Integration Communities (RIC). Host epigenomic data revealed that HIV IS are highly enriched in H3K4met1 and H3K27ac epigenetic marks. Accordingly, we found that HIV-1 target preferentially regulatory elements within the genome namely enhancers and super-enhancers. Our data highlight important features of HIV-1 integration sites that should be considered for the development of strategies for HIV reactivation from latency and the ability of HIV to confer an advantage to infected cells such as clonal expansion.

     

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