Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5' and 3' flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_B54A75B0505D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5' and 3' flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion.
Journal
Nucleic acids research
Author(s)
Csumita M., Csermely A., Horvath A., Nagy G., Monori F., Göczi L., Orbea H.A., Reith W., Széles L.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
24/01/2020
Peer-reviewed
Oui
Volume
48
Number
2
Pages
589-604
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
IRF3, IRF5 and IRF9 are transcription factors, which play distinct roles in the regulation of antiviral and inflammatory responses. The determinants that mediate IRF-specific enhancer selection are not fully understood. To uncover regions occupied predominantly by IRF3, IRF5 or IRF9, we performed ChIP-seq experiments in activated murine dendritic cells. The identified regions were analysed with respect to the enrichment of DNA motifs, the interferon-stimulated response element (ISRE) and ISRE half-site variants, and chromatin accessibility. Using a machine learning method, we investigated the predictability of IRF-dominance. We found that IRF5-dominant regions differed fundamentally from the IRF3- and IRF9-dominant regions: ISREs were rare, while the NFKB motif and special ISRE half-sites, such as 5'-GAGA-3' and 5'-GACA-3', were enriched. IRF3- and IRF9-dominant regions were characterized by the enriched ISRE motif and lower frequency of accessible chromatin. Enrichment analysis and the machine learning method uncovered the features that favour IRF3 or IRF9 dominancy (e.g. a tripartite form of ISRE and motifs for NF-κB for IRF3, and the GAS motif and certain ISRE variants for IRF9). This study contributes to our understanding of how IRF members, which bind overlapping sets of DNA sequences, can initiate signal-dependent responses without activating superfluous or harmful programmes.
Keywords
Animals, Cell Line, Chromatin/genetics, Dendritic Cells/metabolism, Enhancer Elements, Genetic/genetics, Gene Expression Regulation, Humans, Interferon Regulatory Factor-3/genetics, Interferon Regulatory Factors/genetics, Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics, Machine Learning, Mice, NF-kappa B/genetics, Nucleotide Motifs/genetics, Principal Component Analysis, Response Elements/genetics, Transcription Factors/genetics
Pubmed
Web of science
Open Access
Yes
Create date
02/04/2020 18:57
Last modification date
09/08/2024 15:04
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