Induction of type I interferon genes and interferon-inducible genes in embryonal stem cells devoid of interferon regulatory factor 1.
Overexpression of interferon regulatory factor 1 (IRF-1) can induce expression of the interferon (IFN) beta gene, at least in certain cells. A role of IRF-1 in the activation of IFN-alpha genes has also been claimed. We have generated embryonal stem cells in which both IRF-1 alleles were disrupted. In undifferentiated embryonal stem cells, virus-induced levels of IFN-alpha RNA were similar for wild-type and IRF-1%, and there was little induction of IFN-beta RNA in either cell type. In 8-day differentiated cells, the levels of virus-induced IFN-beta RNA, but not of IFN-alpha RNA, were about 10-fold higher than in undifferentiated cells and only slightly higher in wild-type than in IRF-1% cells. Thus, although IRF-1 at high levels may elicit or augment induction of IFN genes under certain circumstances, it is not essential for IFN gene induction by virus. Lack of IRF-1 had no effect on the IFN-induced expression levels of the IFN-inducible genes tested; however, there was little or no constitutive expression of (2'-5')oligoadenylate synthetase in IRF-1% embryonal stem cells, in contrast to wild-type cells.
Ruffner
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Institut für Molekularbiologie I, University of Zürich, Switzerland.
Reis
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Näf
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Weissmann
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D000818:Animals; D002454:Cell Differentiation; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D005786:Gene Expression Regulation; D015698:Genomic Library; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009522:Newcastle disease virus / Q000502:physiology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000502:physiology; D011994:Recombinant Proteins; D015183:Restriction Mapping; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D016898:Interferon-alpha; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D016899:Interferon-beta