E1A Control of Gene Expression Is Mediated by Sequences 5′ to the Transcriptional Starts of the Early Viral Genes

A product of the adenovirus E1A gene is a positive regulator of early viral gene expression. In this report we show that E1A regulates at the transcriptional level and that sequences located 5' to the early viral regions contain sites which confer regulation by the E1A gene product. We constructed chimeric genes in which the sequences at the 5' end of the E2A, E3, and E4 regions were fused to the structural sequences of either the herpes simplex virus thymidine kinase gene, the bacterial gene encoding the enzyme neomycin phosphotransferase, or the chloramphenicol acetyltransferase gene. In all cases, expression of the chimeric genes was induced by a product of the E1A region. It was also found that the insertion of a fragment from the left-hand end of the adenovirus type 5 genome into a plasmid harboring the thymidine kinase gene resulted in elevated frequencies of transformation of TK- cells to TK+. The elevated transformation frequencies were only detected when the insert and tk gene were covalently joined. This effect occurred even when the insert was several kilobase upstream from, and regardless of its orientation to, the transcriptional initiation site of the tk gene. We propose that this region of the adenovirus type 5 genome harbors a cis-acting enhancer of transcription.