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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 10, 2015 |
| Title |
STAT2 and IRF9-dependent IFN-I signaling restores ISRE-mediated transcription and anti-viral activity independent of STAT1 (mouse) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Type I Interferons (IFN-I) mediate cellular responses to virus infection. IFN-I induces IFN-stimulated gene (ISG) expression by phosphorylating STAT1 and STAT2, and together with interferon regulatory factor (IRF9), form the transcription complex ISGF3 that binds to the interferon-stimulated response element (ISRE) in ISG promoters. As a component of ISGF3, it is clear that STAT2 plays an essential role in the transcriptional responses to IFN-I with a strong dependence on STAT1. Previously, we showed that STAT2 also forms homodimers that interact with IRF9 (STAT2-IRF9) to activate transcription of ISRE-containing ISGs in response to IFN-I. Indeed, evidence is accumulating for the existence of a STAT1-independent IFN-I signaling pathway, where STAT2-IRF9 can substitute the role of ISGF3. Here, we provide further insight in the transcriptional regulation and the biological implications of STAT2-IRF9 dependent IFN-I signaling. In human STAT1 KO cells overexpressing human STAT2 (U3C-STAT2), we observed that in response to IFN-I, STAT2 homodimers interact with IRF9 to regulate ISG transcription. The IFN-I-induced phosphorylation profile of STAT2 in U3C-STAT2 was prolonged as compared to WT cells (2fTGH), which corresponded with the expression pattern of OAS2 that also depended on IRF9. Subsequent microarray analysis of IFN-I treated 2fTGH and U3C-STAT2 extended our initial observations and identified more than 60 known antiviral ISGs commonly up-regulated in both cell types. The expression profile of these ISGs was delayed and prolonged in U3C-STAT2 as opposed to the early and transient response in 2fTGH. Moreover, U3C-STAT2 were able to restore an antiviral response upon EMCV and VSV infection that was comparable to the response in 2fTGH. Together, our results strongly suggest that an alternative IFN-I-mediated, STAT2-IRF9 dependent signaling pathway exists that can generate an antiviral response without STAT1 and could be beneficial for example against viruses that directly block STAT1 and impair the formation of ISGF3.
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| Overall design |
Overall, 16 samples were analyzed. MEF wild type cells were treated with IFNalpha at 0h, 4h, 8h, and 24h in duplicates. MEF ST1 KO mST2 cells stably overexpressing mouse STAT2 were treated with IFNalpha at 0h, 4h, 8h, 24h in duplicates. Time point 0h was used as a reference sample.
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| Contributor(s) |
Blaszczyk K, Olejnik A, Chmielewski S, Kostyrko K, Wesoly J, Lee C, Bluyssen HA |
| Citation(s) |
25564224 |
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| Submission date |
Aug 02, 2013 |
| Last update date |
Sep 10, 2015 |
| Contact name |
Hans Bluyssen |
| E-mail(s) |
johannes.bluijssen@amu.edu.pl
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| Organization name |
Faculty of Biology, University of Adam Mickiewicz
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| Department |
Department of Human Molecular Genetics
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| Street address |
Umultowska 89
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| City |
Poznań |
| ZIP/Postal code |
61-614 |
| Country |
Poland |
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| Platforms (1) |
| GPL15097 |
Illumina MouseRef-8 v2.0 expression beadchip (ILMN_GENE) |
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| Samples (16)
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| GSM1200460 |
MEF WT 4h, rep2 |
| GSM1200461 |
MEF WT 8h, rep1 |
| GSM1200462 |
MEF WT 8h, rep2 |
| GSM1200463 |
MEF WT 24h, rep1 |
| GSM1200464 |
MEF WT 24h, rep2 |
| GSM1200465 |
MEF ST1 KO mST2 0h, rep1 |
| GSM1200466 |
MEF ST1 KO mST2 0h, rep2 |
| GSM1200467 |
MEF ST1 KO mST2 4h, rep1 |
| GSM1200468 |
MEF ST1 KO mST2 4h, rep2 |
| GSM1200469 |
MEF ST1 KO mST2 8h, rep1 |
| GSM1200470 |
MEF ST1 KO mST2 8h, rep2 |
| GSM1200471 |
MEF ST1 KO mST2 24h, rep1 |
| GSM1200472 |
MEF ST1 KO mST2 24h, rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE50007 |
STAT2 and IRF9-dependent IFN-I signaling restores ISRE-mediated transcription and anti-viral activity independent of STAT1 |
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| Relations |
| BioProject |
PRJNA214106 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49525_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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