한빛사논문
Ruoyu Wang1,2,6, Joo-Hyung Lee1,6, Jieun Kim3,4, Feng Xiong1, Lana Al Hasani1,2, Yuqiang Shi1, Erin N. Simpson1,2, Xiaoyu Zhu1, Yi-Ting Chen1,2, Pooja Shivshankar1,3,4, Joanna Krakowiak1, Yanyu Wang3,4, David M. Gilbert 5, Xiaoyi Yuan3,4, Holger K. Eltzschig 2,3,4 & Wenbo Li 1,2
1Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
2The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
3Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
4Center for Perioperative Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
5Laboratory of Chromosome Replication and Epigenome Regulation, San Diego Biomedical Research Institute, San Diego, CA, USA.
6These authors contributed equally: Ruoyu Wang, Joo-Hyung Lee.
Corresponding author : Correspondence to Wenbo Li.
Abstract
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.
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