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| Item Type: | Article |
|---|---|
| Title: | Loss of structural specificity in 3D genome organization upon viral infection is predicted by polymer physics |
| Creators: |
Fontana, A.  ORCID: https://orcid.org/0009-0004-1996-4800, Bianco, S. ORCID: https://orcid.org/0000-0001-5819-060X, Tafuri, F., Esposito, A. ORCID: https://orcid.org/0000-0002-5903-8439, Abraham, A., Conte, M. ORCID: https://orcid.org/0000-0002-6670-9800, Vercellone, F., Di Pierno, F. ORCID: https://orcid.org/0009-0009-1042-082X, Kundu, S. ORCID: https://orcid.org/0000-0003-2099-1270, Guha, S. ORCID: https://orcid.org/0000-0003-4376-0731, Di Carluccio, C., Prisco, A., Nicodemi, M. ORCID: https://orcid.org/0000-0002-8416-6416 and Chiariello, A.M. ORCID: https://orcid.org/0000-0002-6112-0167
|
| Abstract: | In the last years, it has been proved that some viruses are able to re-structure chromatin organization and alter the epigenomic landscape of the host genome. In addition, they are able to affect the physical mechanisms shaping chromatin 3D structure, with a consequent impact on gene activity. Here, we investigate with polymer physics genome re-organization of the host genome upon SARS-CoV-2 viral infection and how it can impact structural variability within the population of single-cell chromatin configurations. Using published Hi-C data and molecular dynamics simulations, we build ensembles of 3D configurations representing single-cell chromatin conformations in control and SARS-CoV-2 infected conditions. We focus on genomic length scales of TADs and consider, as a case study, models of real loci containing DDX58 and IL6 genes, belonging, respectively, to the antiviral interferon response and pro-inflammatory genes. Clustering analysis applied to the ensemble of polymer configurations reveals a generally increased variability and a more heterogeneous population of 3D structures in infected conditions. This points toward a scenario in which viral infection leads to a loss of chromatin structural specificity with, likely, a consequent impact on the correct regulation of host cell genes. |
| Keywords: | COVID-19, Chromatin, Human Genome, Molecular Dynamics Simulation, Polymers, SARS-CoV-2 |
| Source: | Journal of Chemical Physics |
| ISSN: | 0021-9606 |
| Publisher: | American Institute of Physics |
| Volume: | 162 |
| Number: | 1 |
| Page Range: | 014903 |
| Date: | 7 January 2025 |
| Official Publication: | https://doi.org/10.1063/5.0243454 |
| PubMed: | View item in PubMed |
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