Genomics

Dataset Information

12

IKK-epsilon regulates the balance between the type I and type II interferon responses


ABSTRACT: 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. ChIP-seq libraries were constructed with an antibody targeting STAT1 from bone marrow macrophages treated with interferon

ORGANISM(S): Mus musculus  

SUBMITTER: S Ng   J Gertz  Jason Gertz 

PROVIDER: E-GEOD-33913 | ArrayExpress | 2011-12-01

SECONDARY ACCESSION(S): SRP009465GSE33913PRJNA148251

REPOSITORIES: GEO, ArrayExpress, ENA

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E-GEOD-33913.idf.txt Idf
E-GEOD-33913.processed.1.zip Processed
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Publications

IκB kinase epsilon (IKK(epsilon)) regulates the balance between type I and type II interferon responses.

Ng Sze-Ling SL   Friedman Brad A BA   Schmid Sonja S   Gertz Jason J   Myers Richard M RM   Tenoever Benjamin R BR   Maniatis Tom T  

Proceedings of the National Academy of Sciences of the United States of America 20111214 52


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-α and IFN-β) induces the assembly of IFN-stimulated gene factor 3 (ISGF3), a multimeric transcriptional activation complex composed of STAT1, STAT2, and IFN regulatory factor 9. IFN-II (IFN-γ) induces the homodimerization of STAT1 to form the gamma-activated factor (GAF) complex. ISGF3 and GAF bind specifically to unique regulatory DNA sequences l  ...[more]

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