Identification of two distinct regulatory regions adjacent to the human beta-interferon gene.
To study the regulation of the human beta-interferon (beta-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 beta-IFN structural gene with 210 bp of DNA to the 5' side of its mRNA cap site (denoted -210), human beta-IFN mRNA is induced approximately 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.
D001483:Base Sequence; D052688:Bovine papillomavirus 1; D002472:Cell Transformation, Viral; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D009154:Mutation; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
D007370:Interferon Type I; D012333:RNA, Messenger; D004247:DNA; D011070:Poly I-C