Zeitschriftenaufsatz
|
2019
A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription
Autor:in
Platanitis, Ekaterini; demiroz, duygu; Schneller, Anja; Fischer, Katrin; Capelle, Christophe M.; Hartl, Markus; Gossenreiter, Thomas; Mueller, Mathias; Novatchkova, M.; Decker, Thomas
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
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-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.
Schlagwörter
Animals; Female; Gene Expression Regulation; Humans; Interferon-Stimulated Gene Factor 3geneticsmetabolism; Interferon-Stimulated Gene Factor 3, gamma Subunitgeneticsmetabolism; Interferonsmetabolism; Macrophagesmetabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Promoter Regions, Genetic; RAW 264.7 Cells; STAT1 Transcription Factorgeneticsmetabolism; STAT2 Transcription Factorgeneticsmetabolism; Transcription, Genetic
Dokumententyp
Originalarbeit
CC Lizenz
CCBY
Open Access Type
Gold
ISSN/eISSN
2041-1723 -
10.1038/s41467-019-10970-y
WoS ID
PubMed ID