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| Status |
Public on Dec 01, 2011 |
| Title |
IKK-epsilon regulates the balance between the type I and type II interferon responses |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Virus infection induces the production of type I and type II interferons (IFN-I and IFN-II), cytokines that mediate the antiviral response. IFN-I (IFN-a and -b) induces the assembly of ISGF3 (interferon-stimulated gene factor 3), a multimeric transcriptional activation complex comprised of STAT1, STAT2 and IRF9. IFN-II (IFN-g) induces the homodimerization of STAT1 to form the GAF (gamma-activated factor) complex. ISGF3 and GAF bind specifically to distinct regulatory DNA sequences located upstream of IFN-I and II inducible genes, respectively, and activate the expression of distinct set of antiviral genes. The balance between the type I and type II IFN pathways plays a critical role in orchestrating the innate and adaptive immune systems. Here, we show that the phosphorylation of STAT1 by IKKε (IkB-related kinase epsilon) inhibits STAT1 homodimerization, and thus GAF formation, but does not disrupt ISGF3 formation. Therefore, virus and/or IFN-I activation of IKKε suppresses GAF-dependent transcription and promotes ISGF3-dependent transcription. In the absence of IKKε, GAF-dependent transcription is enhanced at the expense of ISGF3-mediated transcription, rendering cells less resistant to infection. We conclude that IKKε plays a critical role in regulating the balance between the IFN-I and IFN-II signaling pathways.
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| Overall design |
ChIP-seq libraries were constructed with an antibody targeting STAT1 from bone marrow macrophages treated with interferon
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| Contributor(s) |
Gertz J, Ng S |
| Citation(s) |
22171011 |
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| Submission date |
Nov 23, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason Gertz |
| E-mail(s) |
[email protected]
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| Organization name |
HudsonAlpha Institute
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| Street address |
601 Genome Way
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| City |
Huntsville |
| State/province |
AL |
| ZIP/Postal code |
35806 |
| Country |
USA |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (12)
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| Relations |
| SRA |
SRP009465 |
| BioProject |
PRJNA148251 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33913_RAW.tar |
2.2 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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