Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3.
A 39-nt DNA sequence, the interferon gamma (IFN-gamma) response region (GRR), is necessary for the IFN-gamma-induced transcription of the high-affinity Fc receptor for IgG (Fc gamma RI) and sufficient for the IFN-gamma-induced transcription of transfected plasmids. By using extracts from IFN-gamma-treated cells, three protein complexes will assemble in vitro on a 9-nt core region in the 3' domain of the GRR. The sequence of this core resembles the IFN-gamma-activated sequence (GAS) described for the GBP gene. Mutations in this GAS core region prevent complex assembly and result in the loss of IFN-gamma induction of reporter constructs containing the mutation. In addition to the GAS core region, a 5' region of the GRR is necessary for optimal IFN-gamma induction and for formation of one of the DNA-protein complexes. By antibody reactivity, we show that a 91-kDa protein, first identified as a component of ISGF3, the IFN-alpha-induced transcription complex, is present in at least two of the DNA-protein complexes. IFN-alpha can induce the formation of the faster-migrating 91-kDa protein-GAS complex but not the slower-migrating complex. Furthermore, IFN-alpha does not result in appreciable transcriptional activation of Fc gamma RI or constructs containing the GRR. Thus, these data demonstrate that the IFN-gamma-activated 91-kDa protein is required for IFN-gamma induction of Fc gamma RI and suggest that an additional complex may be required for optimal expression and specificity.
Pearse
R N
RN
DeWitt Wallace Research Laboratory, Division of Molecular Biology, Sloan-Kettering Institute, New York, NY 10021.
Feinman
R
R
Shuai
K
K
Darnell
J E
JE
Ravetch
J V
JV
D000918:Antibody Specificity; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D000077190:Interferon alpha-2; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D007074:Immunoglobulin G; D000077190:Interferon alpha-2; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014157:Transcription Factors; D007371:Interferon-gamma