RT Journal Article SR Electronic T1 Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 287896 DO 10.1101/287896 A1 Lucic, Bojana A1 Chen, Heng-Chang A1 Kuzman, Maja A1 Zorita, Eduard A1 Wegner, Julia A1 Minneker, Vera A1 Roukos, Vassilis A1 Wang, Wei A1 Fronza, Raffaele A1 Schmidt, Manfred A1 Benkirane, Monsef A1 Stadhouders, Ralph A1 Vlahovicek, Kristian A1 Filion, Guillaume J A1 Lusic, Marina YR 2018 UL http://biorxiv.org/content/early/2018/03/24/287896.abstract 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.