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Identification of a FOXO3/IRF7 circuit that limits inflammatory sequelae of antiviral responses (ChIP-Seq)

ABSTRACT: We predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway. C57BL/6 mice were obtained from Jackson Laboratories. Foxo3-/- mice in the FVB background were obtained from MMRRC and were backcrossed to C57BL/6 mice at least 5 times to generate congenic mice. C57BL/6 Foxo3+/- heterozygotes were intercrossed to generate Foxo3-/- mice. Mice were maintained at the animal facility of the Institute for Systems Biology and used at 8–12 weeks of age. All animals were housed and handled according to the approved protocols of University of Washington and Institute for Systems Biology's Institutional Animal Care and Use Committees.

ORGANISM(S): Mus musculus  

SUBMITTER: Vladimir Litvak   Ayush Raman 

PROVIDER: E-GEOD-36241 | ArrayExpress | 2012-09-19



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A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses.

Litvak Vladimir V   Ratushny Alexander V AV   Lampano Aaron E AE   Schmitz Frank F   Huang Albert C AC   Raman Ayush A   Rust Alistair G AG   Bergthaler Andreas A   Aitchison John D JD   Aderem Alan A  

Nature 20120916 7420

Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex int  ...[more]

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