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| Item Type: | Article |
|---|---|
| Title: | Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19 |
| Creators Name: | Zhang, B. and Zhang, Z. and Koeken, V.A.C.M. and Kumar, S. and Aillaud, M. and Tsay, H.C. and Liu, Z. and Kraft, A.R.M. and Soon, C.F. and Odak, I. and Bošnjak, B. and Vlot, A. and Swertz, M.A. and Ohler, U. and Geffers, R. and Illig, T. and Huehn, J. and Saliba, A.E. and Sander, L.E. and Förster, R. and Xu, C.J. and Cornberg, M. and Schulte, L.N. and Li, Y. |
| Abstract: | SARS-CoV-2 infection causes severe COVID-19 in some patients and mild in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified genes that were potentially regulated by differential chromatin accessibility. Then, sub-clustering and motif-enrichment analyses reveals disease condition-specific regulation by transcription factors and their targets, including an interaction between (C/EBPs) and a long-noncoding RNA (LUCAT1), which we validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (AsoC) in COVID-19 patients and identified a SNP rs6800484-C, which is associated with lower expression of (CCR2) and may contribute to higher viral loads and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to COVID-19. |
| Source: | Cell Genomics |
| ISSN: | 2666-979X |
| Publisher: | Cell Press |
| Volume: | 3 |
| Number: | 2 |
| Page Range: | 100232 |
| Date: | 8 February 2023 |
| Official Publication: | https://doi.org/10.1016/j.xgen.2022.100232 |
| PubMed: | View item in PubMed |
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