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  A Multi-Omics Approach Reveals Features That Permit Robust and Widespread Regulation of IFN-Inducible Antiviral Effectors

Goczi, L., Csumita, M., Horvath, A., Nagy, G., Poliska, S., Pigni, M., et al. (2022). A Multi-Omics Approach Reveals Features That Permit Robust and Widespread Regulation of IFN-Inducible Antiviral Effectors. The Journal of Immunology, 209(10), 1930-1941. doi:10.4049/jimmunol.2200363.

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 Creators:
Goczi, Lorand1, Author
Csumita, Maria1, Author
Horvath, Attila1, Author
Nagy, Gergely1, Author
Poliska, Szilard1, Author
Pigni, Matteo1, Author
Thelemann, Christoph1, Author
Daniel, Bence1, Author
Mianesaz, Hamidreza1, Author
Varga, Tamas1, Author
Sen, Kaushik1, Author
Raghav, Sunil K.1, Author
Schoggins, John W.1, Author
Nagy, Laszlo1, Author
Acha-Orbea, Hans1, Author
Meissner, Felix2, Author           
Reith, Walter1, Author
Szeles, Lajos1, Author
Affiliations:
1external, ou_persistent22              
2Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: INTERFERON-STIMULATED GENES; TRANSCRIPTIONAL ACTIVATION; IFITM PROTEINS; RECOGNITION; BINDING; MACROPHAGE; EXPRESSION; INDUCTION; STAT; RESPONSESImmunology;
 Abstract: 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.

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Language(s): eng - English
 Dates: 2022-12-152022
 Publication Status: Issued
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000911413900013
DOI: 10.4049/jimmunol.2200363
 Degree: -

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Title: The Journal of Immunology
  Other : J. Immunol.
Source Genre: Journal
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Publ. Info: Baltimore, U.S.A. : Williams & Wilkins
Pages: - Volume / Issue: 209 (10) Sequence Number: - Start / End Page: 1930 - 1941 Identifier: ISSN: 0022-1767
CoNE: https://pure.mpg.de/cone/journals/resource/954925414915_1