Interactions of α- and γ-interferon in the transcriptional regulation of the gene encoding a guanylate-binding protein

Abstract

Transciptional regulation of the gene encoding a guanylate-binding protein (GBP) by the two interferon (IFN) types was studied. GBP gene transcription was regulated by αIFN in a manner identical to that of previously described IFN-stimulated genes (ISGs): rapid induction, without a need for protein synthesis, followed by a protein synthesis-dependent suppression of transcription to basal levels within 6 h. Transcriptional induction by γIFN was equally rapid and independent of ongoing protein synthesis but remained at elevated levels for >24 h. Experiments employing combined treatments with IFNs of both types revealed that induction of the GBP gene by γIFN overrides the αIFN-induced active repression and reverses the αIFN-induced repressed state. Moreover, the αIFN-mediated repression of ISG54, a gene normally responsive to only αIFN, is also reversed by γIFN. Induction of GBP by γIFN is presumably mediated by a factor different from the recently described activator Interferon Stimulated Gene Factor 3 (ISGF3) because induction of this factor was not observed upon treatment of cells with γIFN. Finally, a complex set of reinforcing or synergistic effects were observed when induction of the GBP gene was evoked by a combined treatment with the two IFN types.