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bioRxiv · 10.1101/377275

Homeostatic and Interferon-induced gene expression represent different states of promoter-associated transcription factor ISGF3

Platanitis, E.·Demiroz, D.·Capelle, C.·Schneller, A.·Hartl, M.·Gossenreiter, T.·Mueller, M.·Novatchkova, M.·Decker, T.
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Abstract

Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signalling cascades, including the JAK-STAT pathway. Our understanding how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. We used 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, unexpectedly, IFN{gamma} 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.

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Platanitis, E., Demiroz, D., Capelle, C., Schneller, A., Hartl, M., Gossenreiter, T., Mueller, M., Novatchkova, M., Decker, T.. 2018-07-25. Homeostatic and Interferon-induced gene expression represent different states of promoter-associated transcription factor ISGF3. https://doi.org/10.1101/377275

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