Loss of structural specificity in 3D genome organization upon viral infection is predicted by polymer physics

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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 Name:	Fontana, A., Bianco, S., Tafuri, F., Esposito, A., Abraham, A., Conte, M., Vercellone, F., Di Pierno, F., Kundu, S., Guha, S., Di Carluccio, C., Prisco, A., Nicodemi, M. and Chiariello, A.M.
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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