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A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription

Author

Listed:
  • Ekaterini Platanitis

    (University of Vienna)

  • Duygu Demiroz

    (University of Vienna)

  • Anja Schneller

    (University of Vienna)

  • Katrin Fischer

    (University of Vienna)

  • Christophe Capelle

    (University of Vienna)

  • Markus Hartl

    (University of Vienna)

  • Thomas Gossenreiter

    (University of Vienna)

  • Mathias Müller

    (University of Veterinary Medicine Vienna)

  • Maria Novatchkova

    (Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)
    Vienna Biocenter (VBC))

  • Thomas Decker

    (University of Vienna)

Abstract

Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. Here, we use an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and IFN-γ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA.

Suggested Citation

  • Ekaterini Platanitis & Duygu Demiroz & Anja Schneller & Katrin Fischer & Christophe Capelle & Markus Hartl & Thomas Gossenreiter & Mathias Müller & Maria Novatchkova & Thomas Decker, 2019. "A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10970-y
    DOI: 10.1038/s41467-019-10970-y
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    Cited by:

    1. Samira Schiefer & Benjamin G. Hale, 2024. "Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Dario Zimmerli & Chiara S. Brambillasca & Francien Talens & Jinhyuk Bhin & Renske Linstra & Lou Romanens & Arkajyoti Bhattacharya & Stacey E. P. Joosten & Ana Moises Silva & Nuno Padrao & Max D. Welle, 2022. "MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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