DIFFERENT PATHWAYS MEDIATE VIRUS INDUCIBILITY OF THE HUMAN IFN-ALPHA-1 AND IFN-BETA GENES

Multimerization of GAAANN generates sequences frequent in virus-inducible promoters. We distinguished different types of (GAAANN)4 sequences mediating virus inducibility. Type I (NN = GT, GC, CT, or CC) responds to IFNs and to IRF-1 and causes silencing. Type II (NN = TG) and type III (NN = CG) neither silence nor respond to IRF-1 or IFN. Type III mediates constitutive transcription and binds the constitutive IEFga factor, whereas type II binds the novel "TG protein‡. IFN-β and IFN-α1 promoters contain different response elements: The former has a type I-like sequence (PRDI) and an NF-κB-binding sequence (PRDII); the latter has a type II-like "TG sequence" and possibly additional elements but does not bind NF-κB. Type I, type II, and NF-κB elements represent three distinct terminal pathways mediating virus induction. © 1990.