STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling
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 coop...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2014
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| Online Access: | https://eprints.nottingham.ac.uk/35709/ |
| _version_ | 1848795143239368704 |
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| author | Begitt, Andreas Droescher, Mathias Meyer, Thomas Schmid, Christoph D. Baker, Michelle Antunes, Filipa Owen, Markus R. Naumann, Ronald Decker, Thomas Vinkemeier, Uwe |
| author_facet | Begitt, Andreas Droescher, Mathias Meyer, Thomas Schmid, Christoph D. Baker, Michelle Antunes, Filipa Owen, Markus R. Naumann, Ronald Decker, Thomas Vinkemeier, Uwe |
| author_sort | Begitt, Andreas |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T19:27:24Z |
| format | Article |
| id | nottingham-35709 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:27:24Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-357092020-05-04T16:41:52Z https://eprints.nottingham.ac.uk/35709/ 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 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. Nature Publishing Group 2014-01-12 Article PeerReviewed 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 http://www.nature.com/ni/journal/v15/n2/full/ni.2794.html doi:10.1038/ni.2794 doi:10.1038/ni.2794 |
| spellingShingle | Begitt, Andreas Droescher, Mathias Meyer, Thomas Schmid, Christoph D. Baker, Michelle Antunes, Filipa Owen, Markus R. Naumann, Ronald Decker, Thomas Vinkemeier, Uwe STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title | STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title_full | STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title_fullStr | STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title_full_unstemmed | STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title_short | STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling |
| title_sort | stat1-cooperative dna binding distinguishes type 1 from type 2 interferon signaling |
| url | https://eprints.nottingham.ac.uk/35709/ https://eprints.nottingham.ac.uk/35709/ https://eprints.nottingham.ac.uk/35709/ |