FUNCTIONAL DIFFERENCES IN THE PROMOTERS OF THE INTERFERON-INDUCIBLE (2'-5')A OLIGOADENYLATE SYNTHETASE AND 6-16-GENES IN INTERFERON-RESISTANT DAUDI CELLS

A clone of interferon-alpha-resistant (IFNr) Daudi cells retained much greater transcriptional inducibility of the (2'-5') oligoadenylate sy nthetase than the 6-16 gene despite the fact that the response of both genes is mediated by highly similar interferon-stimulable DNA respons e elements (ISRE). The primary IFN-alpha activatable transcription fac tor E (ISGF3) and the additional IFN-alpha-inducible ISRE-binding comp lex M were greatly reduced in the IFNr cells. The defect in E was in t he E(alpha) subunit. In electrophoretic mobility-shift assays the 6-16 and (2'-5') oligoadenylate synthetase ISRE competed approximately equ ivalently for E and M. Moreover although active in wild-type cells the (2'-5') oligoadenylate synthetase ISRE was no more capable of conferr ing inducibility on a reporter gene in the IFNr cells than was the 6-1 6 ISRE. The contrasting response of the endogenous (2'-5') oligoadenyl ate synthetase and 6-16 genes in the IFNr cells is, therefore, unlikel y simply to reflect the slight difference in the sequence of their ISR E. Consistent with this, in addition to the ISRE, sequences 5' to the ISRE in the (2'-5') oligoadenylate synthetase promoter appeared necess ary for good induction by IFN alpha in the IFNr cells. Subtle quantita tive changes in the phenotype of the IFNr cells have, however, preclud ed a more precise definition of the DNA element(s) involved.