Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene.

2.50
Hdl Handle:
http://hdl.handle.net/10033/20656
Title:
Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene.
Authors:
Ramsauer, Katrin; Farlik, Matthias; Zupkovitz, Gordin; Seiser, Christian; Kröger, Andrea ( 0000-0002-3131-6580 ) ; Hauser, Hansjörg; Decker, Thomas
Abstract:
A subgroup of genes induced by IFN-gamma requires both STAT1 and IRF1 for transcriptional activation. Using WT, stat1(-/-), or irf1(-/-) cells, we analyzed the changes induced by IFN-gamma in gbp2 promoter chromatin. STAT1 associated with the promoter independently of IRF1 and played an essential role in the ordered recruitment of the coactivator/histone acetyl transferase CREB-binding protein (CBP) and the histone deacetylase HDAC1. Hyperacetylation of histone 4 also required STAT1. Phosphorylation at S727 in the transactivating domain increased transcriptional activity of STAT1. In cells expressing a STAT1S727A-mutant CBP recruitment, histone 4 hyperacetylation and RNA polymerase II association with the gbp2 promoter were strongly reduced. IRF1 association with the gbp2 promoter followed that of STAT1, but STAT1 association with DNA or histone hyperacetylation were not necessary for IRF1 binding. RNA polymerase II association with the gbp2 promoter required both STAT1 and IRF1, suggesting that both proteins mediate essential steps in transcriptional activation. IRF1, but not STAT1, was found to coimmunoprecipitate with RNA polymerase II. Together, the data support the assumption that the main role of STAT1 in activating gbp2 transcription is to provide transcriptionally competent chromatin, whereas the function of IRF1 may lie in directly contacting RNA polymerase II-containing transcriptional complexes.
Affiliation:
Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, A1030 Vienna, Austria.
Citation:
Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. 2007, 104 (8):2849-54 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
20-Feb-2007
URI:
http://hdl.handle.net/10033/20656
DOI:
10.1073/pnas.0610944104
PubMed ID:
17293456
Type:
Article
Language:
en
ISSN:
0027-8424
Appears in Collections:
publications of the research group immunity and infection (IMMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorRamsauer, Katrinen
dc.contributor.authorFarlik, Matthiasen
dc.contributor.authorZupkovitz, Gordinen
dc.contributor.authorSeiser, Christianen
dc.contributor.authorKröger, Andreaen
dc.contributor.authorHauser, Hansjörgen
dc.contributor.authorDecker, Thomasen
dc.date.accessioned2008-03-13T12:59:12Zen
dc.date.available2008-03-13T12:59:12Zen
dc.date.issued2007-02-20en
dc.identifier.citationDistinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. 2007, 104 (8):2849-54 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn0027-8424en
dc.identifier.pmid17293456en
dc.identifier.doi10.1073/pnas.0610944104en
dc.identifier.urihttp://hdl.handle.net/10033/20656en
dc.description.abstractA subgroup of genes induced by IFN-gamma requires both STAT1 and IRF1 for transcriptional activation. Using WT, stat1(-/-), or irf1(-/-) cells, we analyzed the changes induced by IFN-gamma in gbp2 promoter chromatin. STAT1 associated with the promoter independently of IRF1 and played an essential role in the ordered recruitment of the coactivator/histone acetyl transferase CREB-binding protein (CBP) and the histone deacetylase HDAC1. Hyperacetylation of histone 4 also required STAT1. Phosphorylation at S727 in the transactivating domain increased transcriptional activity of STAT1. In cells expressing a STAT1S727A-mutant CBP recruitment, histone 4 hyperacetylation and RNA polymerase II association with the gbp2 promoter were strongly reduced. IRF1 association with the gbp2 promoter followed that of STAT1, but STAT1 association with DNA or histone hyperacetylation were not necessary for IRF1 binding. RNA polymerase II association with the gbp2 promoter required both STAT1 and IRF1, suggesting that both proteins mediate essential steps in transcriptional activation. IRF1, but not STAT1, was found to coimmunoprecipitate with RNA polymerase II. Together, the data support the assumption that the main role of STAT1 in activating gbp2 transcription is to provide transcriptionally competent chromatin, whereas the function of IRF1 may lie in directly contacting RNA polymerase II-containing transcriptional complexes.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshChromatinen
dc.subject.meshGTP-Binding Proteinsen
dc.subject.meshGenes, Regulatoren
dc.subject.meshInterferon Regulatory Factor-1en
dc.subject.meshInterferon Type IIen
dc.subject.meshMiceen
dc.subject.meshMutationen
dc.subject.meshPhosphorylationen
dc.subject.meshPhosphoserineen
dc.subject.meshPromoter Regions (Genetics)en
dc.subject.meshProtein Bindingen
dc.subject.meshProtein Structure, Tertiaryen
dc.subject.meshRNA Polymerase IIen
dc.subject.meshRNA, Messengeren
dc.subject.meshSTAT1 Transcription Factoren
dc.subject.meshTrans-Activation (Genetics)en
dc.subject.meshTranscription, Geneticen
dc.titleDistinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene.en
dc.typeArticleen
dc.contributor.departmentMax F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, A1030 Vienna, Austria.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.