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.
Harada
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Willison
K
K
Sakakibara
J
J
Miyamoto
M
M
Fujita
T
T
Taniguchi
T
T
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