Skip to main content

Research Repository

Advanced Search

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

Authors

Mathias Droescher

Thomas Meyer

Christoph D. Schmid

Filipa Antunes

Markus R. Owen

Ronald Naumann

Thomas Decker

UWE VINKEMEIER uwe.vinkemeier@nottingham.ac.uk
Action Medical Research Professor of Cell Biology



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.

Citation

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), https://doi.org/10.1038/ni.2794

Journal Article Type Article
Acceptance Date Nov 18, 2013
Online Publication Date Jan 12, 2014
Deposit Date Aug 4, 2016
Publicly Available Date Mar 28, 2024
Journal Nature Immunology
Print ISSN 1529-2908
Electronic ISSN 1529-2916
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 15
Issue 2
DOI https://doi.org/10.1038/ni.2794
Public URL https://nottingham-repository.worktribe.com/output/721859
Publisher URL http://www.nature.com/ni/journal/v15/n2/full/ni.2794.html