Repression of simian virus 40 early transcription by viral DNA replication in human 293 cells

Abstract

The small DNA tumour virus simian virus 40 (SV40) has served as an excellent model for many studies on the mechanism and control of gene expression in eukaryotic cells. The SV40 early region produces two protein products. One product (large-T antigen) is known both to repress early viral transcription1,2 and to stimulate viral replication3,4 by binding to specific sites in the origin–promoter region5–7. The early promoter has several similarities to other RNA polymerase II promoters, for example, it possesses a TATA box, an upstream element8–10 and an enhancer11,12. However, the SV40 early promoter differs from other known RNA polymerase II promoters in that the origin of viral DNA replication is embedded within it13,14. Here we show that the SV40 early region is expressed at an extremely low level following its introduction ito human 293 cells, contrasting with results observed in a large number of other cell lines15. We show further that the lack of expression is due to repression of transcription from the SV40 early promoter by viral DNA replication which occurs efficiently in 293 cells.