Title (eng)

Dynamic control of gene expression by ISGF3 and IRF1 during IFNβ and IFNγ signaling


Aarathy Ravi Sundar Jose Geetha   Vienna Biocenter Campus / University of Vienna

Thomas Decker   Vienna Biocenter Campus / University of Vienna

Matthias Farlik   Medical University of Vienna

Mathias Müller   University of Veterinary Medicine Vienna

Ekaterini Platanitis   Vienna Biocenter Campus / University of Vienna

Alex Vogt   Evotec

Georg Smesnik   Vienna Biocenter Campus / University of Vienna

Katrin Fischer   Vienna Biocenter Campus / University of Vienna

Olga Babadei   Vienna Biocenter Campus / University of Vienna


Springer Nature

Description (eng)

Type I interferons (IFN-I, including IFNβ) and IFNγ produce overlapping, yet clearly distinct immunological activities. Recent data show that the distinctness of global transcriptional responses to the two IFN types is not apparent when comparing their immediate effects. By analyzing nascent transcripts induced by IFN-I or IFNγ over a period of 48 h, we now show that the distinctiveness of the transcriptomes emerges over time and is based on differential employment of the ISGF3 complex as well as of the second-tier transcription factor IRF1. The distinct transcriptional properties of ISGF3 and IRF1 correspond with a largely diverse nuclear protein interactome. Mechanistically, we describe the specific input of ISGF3 and IRF1 into enhancer activation and the regulation of chromatin accessibility at interferon-stimulated genes (ISG). We further report differences between the IFN types in altering RNA polymerase II pausing at ISG 5’ ends. Our data provide insight how transcriptional regulators create immunological identities of IFN-I and IFNγ

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Transcription Elongation; Regulatory Elements; Macrophage; Interferons; Binding; Stat1; Complex; Alpha; Susceptibility; Identification

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