A Multi-Omics Approach Reveals Features That Permit Robust and Widespread Regulation of IFN-Inducible Antiviral Effectors
| العنوان: | A Multi-Omics Approach Reveals Features That Permit Robust and Widespread Regulation of IFN-Inducible Antiviral Effectors |
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| المؤلفون: | Loránd Göczi, Mária Csumita, Attila Horváth, Gergely Nagy, Szilárd Póliska, Matteo Pigni, Christoph Thelemann, Bence Dániel, Hamidreza Mianesaz, Tamás Varga, Kaushik Sen, Sunil K. Raghav, John W. Schoggins, Laszlo Nagy, Hans Acha-Orbea, Felix Meissner, Walter Reith, Lajos Széles |
| المصدر: | The Journal of Immunology. 209:1930-1941 |
| بيانات النشر: | The American Association of Immunologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Antiviral Restriction Factors, Mice, Immunology, Animals, Immunology and Allergy, Interferons, Nucleotide Motifs, Promoter Regions, Genetic, Response Elements, Chromatin |
| الوصف: | The antiviral state, an initial line of defense against viral infection, is established by a set of IFN-stimulated genes (ISGs) encoding antiviral effector proteins. The effector ISGs are transcriptionally regulated by type I IFNs mainly via activation of IFN-stimulated gene factor 3 (ISGF3). In this study, the regulatory elements of effector ISGs were characterized to determine the (epi)genetic features that enable their robust induction by type I IFNs in multiple cell types. We determined the location of regulatory elements, the DNA motifs, the occupancy of ISGF3 subunits (IRF9, STAT1, and STAT2) and other transcription factors, and the chromatin accessibility of 37 effector ISGs in murine dendritic cells. The IFN-stimulated response element (ISRE) and its tripartite version occurred most frequently in the regulatory elements of effector ISGs than in any other tested ISG subsets. Chromatin accessibility at their promoter regions was similar to most other ISGs but higher than at the promoters of inflammation-related cytokines, which were used as a reference gene set. Most effector ISGs (81.1%) had at least one ISGF3 binding region proximal to the transcription start site (TSS), and only a subset of effector ISGs (24.3%) was associated with three or more ISGF3 binding regions. The IRF9 signals were typically higher, and ISRE motifs were “stronger” (more similar to the canonical sequence) in TSS-proximal versus TSS-distal regulatory regions. Moreover, most TSS-proximal regulatory regions were accessible before stimulation in multiple cell types. Our results indicate that “strong” ISRE motifs and universally accessible promoter regions that permit robust, widespread induction are characteristic features of effector ISGs. |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2200363 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::484682173ce91c6d2f9665737419b0c4 https://doi.org/10.4049/jimmunol.2200363 |
| رقم الانضمام: | edsair.doi.dedup.....484682173ce91c6d2f9665737419b0c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.2200363 |