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Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells

Author

Listed:
  • Andrea M. Chiariello

    (Complesso Universitario di Monte Sant’Angelo)

  • Alex Abraham

    (Complesso Universitario di Monte Sant’Angelo)

  • Simona Bianco

    (Complesso Universitario di Monte Sant’Angelo)

  • Andrea Esposito

    (Complesso Universitario di Monte Sant’Angelo)

  • Andrea Fontana

    (Complesso Universitario di Monte Sant’Angelo)

  • Francesca Vercellone

    (Università degli Studi di Napoli Federico II, and INFN Napoli)

  • Mattia Conte

    (Complesso Universitario di Monte Sant’Angelo)

  • Mario Nicodemi

    (Complesso Universitario di Monte Sant’Angelo
    Berlin Institute for Medical Systems Biology at the Max Delbruck Center for Molecular Medicine in the Helmholtz Association)

Abstract

SARS-CoV-2 can re-structure chromatin organization and alter the epigenomic landscape of the host genome, but the mechanisms that produce such changes remain unclear. Here, we use polymer physics to investigate how the chromatin of the host genome is re-organized upon infection with SARS-CoV-2. We show that re-structuring of A/B compartments can be explained by a re-modulation of intra-compartment homo-typic affinities, which leads to the weakening of A-A interactions and the enhancement of A-B mixing. At the TAD level, re-arrangements are physically described by a reduction in the loop extrusion activity coupled with an alteration of chromatin phase-separation properties, resulting in more intermingling between different TADs and a spread in space of the TADs themselves. In addition, the architecture of loci relevant to the antiviral interferon response, such as DDX58 or IFIT, becomes more variable within the 3D single-molecule population of the infected model, suggesting that viral infection leads to a loss of chromatin structural specificity. Analysing the time trajectories of pairwise gene-enhancer and higher-order contacts reveals that this variability derives from increased fluctuations in the chromatin dynamics of infected cells. This suggests that SARS-CoV-2 alters gene regulation by impacting the stability of the contact network in time.

Suggested Citation

  • Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Andrea Fontana & Francesca Vercellone & Mattia Conte & Mario Nicodemi, 2024. "Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48370-6
    DOI: 10.1038/s41467-024-48370-6
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    References listed on IDEAS

    as
    1. Mattia Conte & Luca Fiorillo & Simona Bianco & Andrea M. Chiariello & Andrea Esposito & Mario Nicodemi, 2020. "Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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