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

Autor: Lucic B; Department of Infectious Diseases, Integrative Virology, Heidelberg University Hospital and German Center for Infection Research, Heidelberg, Germany., Chen HC; Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.; University Pompeu Fabra, Barcelona, Spain., Kuzman M; Bioinformatics Group, Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia., Zorita E; Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.; University Pompeu Fabra, Barcelona, Spain., Wegner J; Department of Infectious Diseases, Integrative Virology, Heidelberg University Hospital and German Center for Infection Research, Heidelberg, Germany.; Institute for Clinical Chemistry and Clinical Pharmacology, Universitätsklinikum Bonn, Bonn, Germany., Minneker V; Institute of Molecular Biology (IMB), Mainz, Germany., Wang W; German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Fronza R; German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Laufs S; German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Schmidt M; German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Stadhouders R; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.; Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands., Roukos V; Institute of Molecular Biology (IMB), Mainz, Germany., Vlahovicek K; Bioinformatics Group, Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia. kristian@bioinfo.hr., Filion GJ; Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain. guillaume.filion@gmail.com.; University Pompeu Fabra, Barcelona, Spain. guillaume.filion@gmail.com.; Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada. guillaume.filion@gmail.com., Lusic M; Department of Infectious Diseases, Integrative Virology, Heidelberg University Hospital and German Center for Infection Research, Heidelberg, Germany. Marina.lusic@med.uni-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Sep 06; Vol. 10 (1), pp. 4059. Date of Electronic Publication: 2019 Sep 06.
DOI: 10.1038/s41467-019-12046-3
Abstrakt: 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.
Databáze: MEDLINE
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