Abstract: |
A 39-nt DNA sequence, the interferon γ (IFN-γ) response region (GRR), is necessary for the IFN-γ-induced transcription of the high-affinity Fc receptor for IgG (FcγRI) and sufficient for the IFN-γ-induced transcription of transfected plasmids. By using extracts from IFN-γ-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-γ-activated sequence (GAS) described for the GBP gene. Mutations in this GAS core region prevent complex assembly and result in the loss of IFN-γ 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-γ 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-γ-induced transcription complex, is present in at least two of the DNA- protein complexes. IFN-α can induce the formation of the faster-migrating 91-kDa protein-GAS complex but not the slower-migrating complex. Furthermore, IFN-α does not result in appreciable transcriptional activation of FcγRI or constructs containing the GRR. Thus, these data demonstrate that the IFN-γ- activated 91-kDa protein is required for IFN-γ induction of FcγRI and suggest that an additional complex may be required for optimal expression and specificity. |