Regulation of a metallothionein-growth hormone hybrid gene in bovine papilloma virus

Abstract

We have constructed bovine papilloma virus recombinants carrying a hybrid gene in which human growth hormone structural sequences are fused to the promoter and presumptive control region of the mouse metallothionein-I gene. Mouse cells transformed with the recombinants synthesize metallothionein-growth hormone hybrid mRNA with the same 5' end as metallothionein mRNA. Hybrid mRNA is inducible by cadmium but not by dexamethasone, whereas the chromosomal metallothionein genes in the same cells are inducible by both agents. This indicates that heavy metals and glucocorticoids regulate the mouse metallothionein-I gene by independent mechanisms. Furthermore, because the transformed cells produce large quantities of human growth hormone polypeptide, it appears that bovine papilloma virus-metallothionein vectors may be useful for obtaining the efficient and regulatable expression of other eukaryotic gene products. We have constructed recombinants that allow the insertion of new structural sequences under the control of the metallothionein promoter.