Enhancer-like interferon responsive sequences of the human and murine (2'-5') oligoadenylate synthetase gene promoters.

The human (2'-5') oligo(A) synthetase gene contains two independent cis-acting DNA elements, A and B, which act as transcriptional enhancers. Element A alone is not activated by IFN treatment. Element B alone confers IFN-inducibility to the herpes tk promoter. Two murine (2'-5') oligo(A) synthetase genes were isolated and their promoter sequences show high conservation of element A and B. A synthetic oligonucleotide, containing 16 bp of the human element B, or 14 bp of the homologue murine element B, was linked to a TK-CAT construct. These oligonucleotides were shown to be sufficient to activate the TK promoter in the presence of IFN. When multiple repeats of the interferon-responsive sequence (E-IRS) were cloned in 5' of the TK promoter, the activation ratio was increased. In vitro, specific binding of nuclear protein(s) is observed to the radiolabelled synthetic human E-IRS. This binding is competed by the addition of cold synthetic mouse E-IRS or fragments of genomic DNA containing the E-IRS.