Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
Interferons (IFNs) are a heterogeneous family of cytokines that exhibits multiple biological activities. Upon viral infection, expression of type I IFNs (i.e., IFN-alpha and IFN-beta) is induced in a variety of differentiated cells but not in cells of embryonal origin. IRF-1 and IRF-2, which bind to the same cis-elements within the promoters of type I IFN and IFN-inducible MHC class I genes, were identified previously. Here we demonstrate that the expression of both IRF and IFN genes is developmentally regulated in mouse EC cells; these genes become functional only after cell differentiation. Furthermore, cDNA-directed IRF-1 produced in undifferentiated but not differentiated EC cells efficiently activates the transfected IFN-alpha and IFN-beta and endogenous IFN-alpha genes, whereas IRF-2 represses the IRF-1 effects. These findings emphasize the dual function of the IRF-responsive cis-elements as positive and negative regulators, since they can be occupied by transcriptionally active or inactive IRF molecules. This type of regulatory mechanism might operate in other cytokine systems.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
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H
Harada
K
K
Willison
J
J
Sakakibara
M
M
Miyamoto
T
T
Fujita
T
T
Taniguchi
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010750:Phosphoproteins / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D013724:Teratoma; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007370:Interferon Type I; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors