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

Author

Listed:
  • Bojana Lucic

    (Heidelberg University Hospital and German Center for Infection Research)

  • Heng-Chang Chen

    (Barcelona Institute of Science and Technology
    University Pompeu Fabra)

  • Maja Kuzman

    (University of Zagreb)

  • Eduard Zorita

    (Barcelona Institute of Science and Technology
    University Pompeu Fabra)

  • Julia Wegner

    (Heidelberg University Hospital and German Center for Infection Research
    Institute for Clinical Chemistry and Clinical Pharmacology, Universitätsklinikum Bonn)

  • Vera Minneker

    (Institute of Molecular Biology (IMB))

  • Wei Wang

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Raffaele Fronza

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Stefanie Laufs

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Manfred Schmidt

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Ralph Stadhouders

    (Erasmus MC
    Erasmus MC)

  • Vassilis Roukos

    (Institute of Molecular Biology (IMB))

  • Kristian Vlahovicek

    (University of Zagreb)

  • Guillaume J. Filion

    (Barcelona Institute of Science and Technology
    University Pompeu Fabra
    University of Toronto Scarborough)

  • Marina Lusic

    (Heidelberg University Hospital and German Center for Infection Research)

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.

Suggested Citation

  • Bojana Lucic & Heng-Chang Chen & Maja Kuzman & Eduard Zorita & Julia Wegner & Vera Minneker & Wei Wang & Raffaele Fronza & Stefanie Laufs & Manfred Schmidt & Ralph Stadhouders & Vassilis Roukos & Kris, 2019. "Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12046-3
    DOI: 10.1038/s41467-019-12046-3
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    Cited by:

    1. Agnieszka Dorman & Maryam Bendoumou & Aurelija Valaitienė & Jakub Wadas & Haider Ali & Antoine Dutilleul & Paolo Maiuri & Lorena Nestola & Monika Bociaga-Jasik & Gilbert Mchantaf & Coca Necsoi & Stéph, 2025. "Nuclear retention of unspliced HIV-1 RNA as a reversible post-transcriptional block in latency," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    2. Miguel M. Álvarez & Josep Biayna & Fran Supek, 2022. "TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Hannah L. Harris & Huiya Gu & Moshe Olshansky & Ailun Wang & Irene Farabella & Yossi Eliaz & Achyuth Kalluchi & Akshay Krishna & Mozes Jacobs & Gesine Cauer & Melanie Pham & Suhas S. P. Rao & Olga Dud, 2023. "Chromatin alternates between A and B compartments at kilobase scale for subgenic organization," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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