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Series GSE33913 Query DataSets for GSE33913
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
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.
Overall design ChIP-seq libraries were constructed with an antibody targeting STAT1 from bone marrow macrophages treated with interferon
Contributor(s) Gertz J, Ng S
Citation(s) 22171011
Submission date Nov 23, 2011
Last update date May 15, 2019
Contact name Jason Gertz
Organization name HudsonAlpha Institute
Street address 601 Genome Way
City Huntsville
State/province AL
ZIP/Postal code 35806
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (12)
GSM838681 WT Stat1 untreated BMM
GSM838682 WT Reverse crosslink untreated BMM
GSM838683 WT Stat1 6hr IFNg BMM
SRA SRP009465
BioProject PRJNA148251

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Supplementary file Size Download File type/resource
GSE33913_RAW.tar 2.2 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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