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

Lucic, Bojana; Chen, Heng-Chang; Kuzman, Maja; Zorita, Eduard; Wegner, Julia; Minneker, Vera; Wang, Wei; Fronza, Raffaele; Laufs, Stefanie; Schmidt, Manfred; Stadhouders, Ralph; Roukos, Vassilis; Vlahovicek, Kristian; Filion, Guillaume; Lusic, Marina

doi:http://dx.doi.org/10.1038/s41467-019-12046-3

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

Llicència

Citació

Lucic B, Chen HC, Kuzman M, Zorita E, Wegner J, Minneker V, Wang W, Fronza R, Laufs S, Schmidt M, Stadhouders R, Roukos V, Vlahovicek K, Filion GJ, Lusic M. Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration. Nat Commun. 2019; 10(1):4059. DOI: 10.1038/s41467-019-12046-3

Resum

HIV-1 recurrently targets active genes and integrates in the proximity of the nuclear pore compartment in CD4+ T cells. 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 proximal to 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 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 provide evidence of the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.