Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon.
Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp-1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1 binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN-gamma requires transcription factor IRF-1. Transient overexpression of IRF-1 cDNA in mouse fibroblasts resulted in high-level expression of Gbp promoter constructs. Unlike wild-type cells, IRF-1% embryonic stem cells lacking functional transcription factor IRF-1 contained very low levels of Gbp transcripts that were not increased in response to differentiation or treatment with IFN-gamma. Treatment of IRF-1% mice with IFN-gamma resulted in barely detectable levels of Gbp RNA in spleens, lungs, and livers, whereas such treatment induced high levels of Gbp RNA in the organs of wild-type mice. These observations suggest two alternative pathways for transcriptional induction of genes in response to IFN-gamma: immediate response that results from activation of preformed Stat1 and delayed response that results from induced de novo synthesis of transcription factor IRF-1.
Briken
V
V
Institut für Mikrobiologie und Hygiene, Abteilung Virologie, University of Freiburg, Germany.
Ruffner
H
H
Schultz
U
U
Schwarz
A
A
Reis
L F
LF
Strehlow
I
I
Decker
T
T
Staeheli
P
P
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D015183:Restriction Mapping; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; C494259:Irf1 protein, rat; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; C494081:Stat1 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins