PT - JOURNAL ARTICLE AU - Lucic, Bojana AU - Chen, Heng-Chang AU - Kuzman, Maja AU - Zorita, Eduard AU - Wegner, Julia AU - Minneker, Vera AU - Roukos, Vassilis AU - Wang, Wei AU - Fronza, Raffaele AU - Schmidt, Manfred AU - Benkirane, Monsef AU - Stadhouders, Ralph AU - Vlahovicek, Kristian AU - Filion, Guillaume J AU - Lusic, Marina TI - Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 AID - 10.1101/287896 DP - 2018 Jan 01 TA - bioRxiv PG - 287896 4099 - http://biorxiv.org/content/early/2018/03/24/287896.short 4100 - http://biorxiv.org/content/early/2018/03/24/287896.full AB - HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are delineated with super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.