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Papers of the Week

Papers: 25 Mar 2023 - 31 Mar 2023

Basic Science



2023 Mar 23

Nat Microbiol


SARS-CoV-2 restructures host chromatin architecture.


Wang R, Lee JH, Kim J, Xiong F, Hasani LA, Shi Y, Simpson EN, Zhu X, Chen YT, Shivshankar P, Krakowiak J, Wang Y, Gilbert DM, Yuan X, Eltzschig HK, Li W


Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes by the virus, while increased H3K4me3 was found in the promoters of pro-inflammatory genes highly induced during severe COVID-19. These findings show that SARS-CoV-2 acutely rewires host chromatin, facilitating future studies of the long-term epigenomic impacts of its infection.