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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2014 (arch)     Display Documents



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ID: 705768.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2014 (arch)
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
Date of Publication (YYYY-MM-DD):2014
Title of Journal:Nature Immunology
Volume:15
Issue / Number:2
Start Page:168
End Page:176
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:thuem
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5637
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