Delimitation and properties of DNA sequences required for the regulated expression of human interferon-beta gene

Abstract

The human interferon-beta (IFN-beta) gene contains sequences within its 5'-flanking region that mediate the virus-induced activation of mRNA transcription. A series of mutant IFN-beta genes, including the 5' deletion mutants, was constructed and introduced into mouse L929 cells. Expression study of those mutant genes demonstrates that: sequences upstream, but not downstream, of -40 from the cap site are responsible for the viral induction of the gene; that the upstream boundary of the DNA sequences required to support the maximum level of induction lies between -117 and -105 from the cap site; and that this upstream sequence shows a property similar to enhancer elements as it functions in either orientation with a latitude in distance from the cap site. Within this sequence, we note the presence of repetitious hexanucleotides (consensus: A-A-AG-TG-G-A), each of which may play a role in the maximum induction of the IFN-beta gene.