Lucic, BojanaChen, Heng-ChangKuzman, MajaZorita, EduardWegner, JuliaMinneker, VeraWang, WeiFronza, RaffaeleLaufs, StefanieSchmidt, ManfredStadhouders, RalphRoukos, VassilisVlahovicek, KristianFilion, GuillaumeLusic, Marina2020-04-032020-04-032019Lucic 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/s41467-019-12046-32041-1723http://hdl.handle.net/10230/44153HIV-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.application/pdfeng© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integrationinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-019-12046-3Chromatin structureComputational biology and bioinformaticsGeneticsNuclear organizationRetrovirusinfo:eu-repo/semantics/openAccess