Loss of structural specificity in 3D genome organization upon viral infection is predicted by polymer physics
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.
Article Details
Journal Info
The Journal of Chemical Physics
American Institute of Physics
Authors (14)
Andrea Fontana
Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
Simona Bianco
Fabrizio Tafuri
Dipartimento di Fisica, Università degli Studi di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo 1 , 80126 Naples,
Andrea Esposito
Alex Abraham
Mattia Conte
Francesca Vercellone
Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale - DICMaPI, Università degli Studi di Napoli Federico II, and INFN Napoli 2 , Piazzale Vincenzo Tecchio 80, 80125 Naples,
Florinda Di Pierno
Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale - DICMaPI, Università degli Studi di Napoli Federico II, and INFN Napoli 2 , Piazzale Vincenzo Tecchio 80, 80125 Naples,
Sumanta Kundu
Dipartimento di Fisica, Università degli Studi di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo 1 , 80126 Naples,
Sougata Guha
Department of Physics, Indian Institute of Technology Bombay , Mumbai 400076, and , Napoli 80126,
Ciro Di Carluccio
Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale - DICMaPI, Università degli Studi di Napoli Federico II, and INFN Napoli 2 , Piazzale Vincenzo Tecchio 80, 80125 Naples,
Antonella Prisco
CNR-IGB 3 , Via Pietro Castellino 111, 80131 Naples,
Mario Nicodemi
Andrea M. Chiariello
Dipartimento di Fisica, Università degli Studi di Napoli Federico II, and INFN Napoli, Complesso Universitario di Monte Sant’Angelo 1 , 80126 Naples,