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PMID: 17293456 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 8 ·2007-02-20 ·Pages 2849-54

Ramsauer K, Farlik M, Zupkovitz G, Seiser C, Kröger A, Hauser H, Decker T

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.

MeSH Terms
Animals Chromatin/drug effects,metabolism GTP-Binding Proteins/genetics Genes, Regulator Interferon Regulatory Factor-1/deficiency,metabolism Interferon-gamma/pharmacology Mice Mutation/genetics Phosphorylation/drug effects Phosphoserine/metabolism Promoter Regions, Genetic/drug effects Protein Binding/drug effects Protein Structure, Tertiary/drug effects RNA Polymerase II/metabolism RNA, Messenger/genetics,metabolism STAT1 Transcription Factor/deficiency,metabolism Transcription, Genetic/drug effects Transcriptional Activation/drug effects
Chemicals
Chromatin Gbp2b protein, mouse Interferon Regulatory Factor-1 Irf1 protein, mouse RNA, Messenger STAT1 Transcription Factor Stat1 protein, mouse Phosphoserine Interferon-gamma RNA Polymerase II GTP-Binding Proteins Gbp2 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ramsauer Katrin
Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, A1030 Vienna, Austria.
Farlik Matthias
Zupkovitz Gordin
Seiser Christian
Kröger Andrea
Hauser Hansjörg
Decker Thomas
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0610944104
Published
2007-02-20
Epub
2007-00-09
Pages
2849-54
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1815270
Subset
IM
Grants
Austrian Science Fund FWF · F 2803 · Austria
External Links
PubMed source DOI: 10.1073/pnas.0610944104 PMC Full Text View journal details
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