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

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• dc.contributor.author Lucic, Bojana
• dc.contributor.author Chen, Heng-Chang
• dc.contributor.author Kuzman, Maja
• dc.contributor.author Zorita, Eduard
• dc.contributor.author Wegner, Julia
• dc.contributor.author Minneker, Vera
• dc.contributor.author Wang, Wei
• dc.contributor.author Fronza, Raffaele
• dc.contributor.author Laufs, Stefanie
• dc.contributor.author Schmidt, Manfred
• dc.contributor.author Stadhouders, Ralph
• dc.contributor.author Roukos, Vassilis
• dc.contributor.author Vlahovicek, Kristian
• dc.contributor.author Filion, Guillaume
• dc.contributor.author Lusic, Marina
• dc.date.accessioned 2020-04-03T07:28:33Z
• dc.date.available 2020-04-03T07:28:33Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.description.sponsorship This work was supported by German Center for Infection Research (DZIF) Thematic Translational Unit HIV-1 04.704 Infrastructural Measure to M.L. and by the Hector Grant M70 “HiPNose: HiV Positioning in the Nuclear Space” to M.L. and M.S. We acknowledge the financial support of the Spanish Ministry of Economy and Competitiveness (“Centro de Excelencia Severo Ochoa 2013–2017,” Plan Nacional BFU2012–37168), of the CERCA (Centres de Recerca de Catalunya) Programme/Generalitat de Catalunya, and of the European Research Council (Synergy Grant 609989). K.V. and M.K. are supported by the European Structural and Investment Funds grant for the Croatian National Centre of Research Excellence in Personalized Healthcare (contract #KK.01.1.1.01.0010), Croatian National Centre of Research Excellence for Data Science and Advanced Cooperative Systems (contract KK.01.1.1.01.0009), and Croatian Science Foundation (grant IP-2014–09–6400).
• dc.format.mimetype application/pdf
• dc.identifier.citation 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
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-12046-3
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/44153
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2019; 10(1):4059
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
• dc.rights © 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Chromatin structure
• dc.subject.keyword Computational biology and bioinformatics
• dc.subject.keyword Genetics
• dc.subject.keyword Nuclear organization
• dc.subject.keyword Retrovirus
• dc.title Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion