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Spatially clustered loci with multiple enhancers are frequent targets of HIV-1

By Bojana Lucic, Heng-Chang Chen, Maja Kuzman, Eduard Zorita, Julia Wegner, Vera Minneker, Vassilis Roukos, Wei Wang, Raffaele Fronza, Manfred Schmidt, Monsef Benkirane, Ralph Stadhouders, Kristian Vlahovicek, Guillaume J Filion, M. Lusic

Posted 24 Mar 2018
bioRxiv DOI: 10.1101/287896 (published DOI: 10.1038/s41467-019-12046-3)

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.

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