title: STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
abstract: STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon.
authors.affiliation: 1] School of Life Sciences, University of Nottingham, Nottingham, UK. [2].
authors.forename: Andreas
authors.initials: A
authors.lastname: Begitt
authors.affiliation: 1] School of Life Sciences, University of Nottingham, Nottingham, UK. [2] [3].
authors.forename: Mathias
authors.initials: M
authors.lastname: Droescher
authors.affiliation: 1] Klinik für Psychosomatische Medizin und Psychotherapie, Universitätsmedizin Göttingen, Göttingen, Germany. [2].
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.affiliation: 1] Swiss Tropical and Public Health Institute, Basel, Switzerland. [2] Universität Basel, Basel, Switzerland.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Schmid
authors.affiliation: Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Baker
authors.affiliation: 1] School of Life Sciences, University of Nottingham, Nottingham, UK. [2].
authors.forename: Filipa
authors.initials: F
authors.lastname: Antunes
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.affiliation: Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Owen
authors.affiliation: Max-Planck-Institut für molekulare Zellbiologie und Genetik, Dresden, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.affiliation: Department für Mikrobiologie und Immunbiologie, Universität Wien, Wien, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Uwe
authors.initials: U
authors.lastname: Vinkemeier
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism*; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D015202:Protein Engineering; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014721:Vesicular stomatitis Indiana virus
chemical_list: D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050505:Mutant Proteins; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D004247:DNA