STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signalingTools Begitt, Andreas, Droescher, Mathias, Meyer, Thomas, Schmid, Christoph D., Baker, Michelle, Antunes, Filipa, Owen, Markus R., Naumann, Ronald, Decker, Thomas and Vinkemeier, Uwe (2014) STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling. Nature Immunology, 15 (2). pp. 168-176. ISSN 1529-2916 Full text not available from this repository.AbstractSTAT1 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.
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