Regulation of two interferon‐inducible human genes by interferon, poly(rI) · poly(rC) and viruses

Abstract

The IFI‐56K and IFI‐54K genes are transcriptionally stimulated when cells are treated by interferon. We have previously shown that the IFI‐56K gene is in addition directly induced by poly(rI) · poly(rC), and inducer of interferon‐β. Since the regulation of the IFI‐56K and IFI‐54K genes by interferon are very much alike, we tested whether the IFI‐54K gene is also directly regulated by poly(rI) · poly(rC). Treatment of various cell lines with poly(rI) · poly(rC) leads to a clear accumulation of the IFI‐54K mRNA to a level which sometimes even exceeds that obtained with high doses of interferon. Several interferon‐resistant cell lines were investigated for the inducibility of both the IFI‐56K and IFI‐54K genes by interferons, poly(rI) · poly(rC) and viruses (which are the natural inducers of interferon‐α and ‐β). Both genes appear to be coordinately regulated by these inducers. It was thus interesting to search for common regulatory element(s) in the control region of these two genes. The IFI‐54K gene promoter region was isolated, from which a 520‐base‐pair segment was sequenced and compared with the promoter region of the IFI‐56K gene that we had previously sequenced. The only homology was found is a well conserved 19‐bp segment located just upstream of the TATA box of these genes; interestingly, this sequence is also homologous to the minimal region needed for the inducibility by poly(rI) · poly(rC) of the interferon‐β gene. This conserved sequence might be responsible for the coordinate induction of the IFI‐56K and IFI‐54K genes by interferon, poly(rI) · poly(rC) and viruses.