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- Title
STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
- Authors
Begitt, Andreas; Droescher, Mathias; Meyer, Thomas; Schmid, Christoph D; Baker, Michelle; Antunes, Filipa; Owen, Markus R; Naumann, Ronald; Decker, Thomas; Vinkemeier, Uwe
- 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.
- Subjects
STAT proteins; DNA-binding proteins; COOPERATIVE binding (Biochemistry); INTERFERONS; CELLULAR signal transduction; GENETIC transcription regulation
- Publication
Nature Immunology, 2014, Vol 15, Issue 2, p168
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2794