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STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling

Begitt, Andreas; Droescher, Mathias; Meyer, Thomas; Schmid, Christoph D.; Baker, Michelle; Antunes, Filipa; Owen, Markus R.; Naumann, Ronald; Decker, Thomas; Vinkemeier, Uwe


Mathias Droescher

Thomas Meyer

Christoph D. Schmid

Filipa Antunes

Markus R. Owen

Ronald Naumann

Thomas Decker

Action Medical Research Professor of Cell Biology


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.


Begitt, A., Droescher, M., Meyer, T., Schmid, C. D., Baker, M., Antunes, F., …Vinkemeier, U. (in press). STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling. Nature Immunology, 15(2), doi:10.1038/ni.2794

Journal Article Type Article
Acceptance Date Nov 18, 2013
Online Publication Date Jan 12, 2014
Deposit Date Aug 4, 2016
Journal Nature Immunology
Print ISSN 1529-2908
Electronic ISSN 1529-2916
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 15
Issue 2
Public URL
Publisher URL
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