The alpha promoter regulator-ovalbumin chimeric gene resident in human cells is regulated like the authentic alpha 4 gene after infection with herpes simplex virus 1 mutants in alpha 4 gene.

Human TK- 143 cells were converted to TK+ phenotype with a plasmid containing the native herpes simplex virus 1 (HSV-1), thymidine kinase, a beta gene, and a chimeric ovalbumin gene consisting of the coding sequences of the ovalbumin gene linked to the promoter-regulatory region of the HSV-1 alpha 4 gene. Comparison of the synthesis of ovalbumin and the alpha 4 gene product in the converted cells infected with ts mutants in alpha 4 gene and incubated at the permissive (33 degrees C) and nonpermissive (39 degrees C) temperatures revealed the following. (i) The synthesis of both ovalbumin and alpha 4 gene product was transiently induced at the permissive temperature but continued at elevated levels for many hours at the nonpermissive temperature. (ii) The synthesis of both ovalbumin and alpha 4 gene products resumed when the infected cells were shifted from permissive to nonpermissive temperature after the shut-off of alpha protein synthesis. (iii) Although both the beta-TK and alpha 4-ovalbumin chimeric genes were covalently linked on the same plasmid, each was regulated independently. We conclude that alpha gene regulation is determined solely by (a) the inducer and (b) the induction sequence contained in the promoter-regulatory region and not by the location or the higher order structure of the immediate environment of the gene.