Identification of two distinct regulatory regions adjacent to the human β-interferon gene

Abstract

To study the regulation of the human β-interferon (β-IFN) gene by poly(I)-poly(C), we analyzed the expression of deletion mutants of the cloned gene introduced into mouse cells on a new bovine papilloma virus (BPV) vector. In stable cell lines transformed by a BPV-IFN plasmid containing the β-IFN structural gene with 210 bp of DNA to the 5′ side of its mRNA cap site (denoted −210), human β-IFN mRNA is induced ∼400-fold by poly(I)-poly(C), and reproducible levels of expression are observed for independent cell lines. Our studies indicate that there are two distinct regulatory regions adjacent to the gene, located between −77 and −19, and between −210 and −107. The −77 to −19 region is required for constitutive and induced IFN gene expression, and both are drastically reduced by deletion to −73. When sequences between −210 and −107 are deleted, the constitutive level of IFN gene expression is increased 5- to 10-fold, while induced expression is essentially unaffected. Deletion of the −210 to −107 region also alters the kinetics of induction of the gene.

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