Cell- and promoter-specific activation of transcription by DNA replication.

To study the effects that DNA replication can exert on transcription in mammalian cells, we have analyzed transient expression from the adenovirus major late promoter contained on replicating and nonreplicating plasmids in several cell types. When a 100-bp fragment containing the late promoter was used to direct expression of the simian virus 40 (SV40) early region, efficient transcription could be detected that was only slightly enhanced when a functional origin of replication was included in the plasmid. In contrast with this, and with similar findings using related late promoter-containing plasmids, expression from this promoter was absolutely dependent on DNA replication when it was inserted in the region of SV40 DNA encoding the late mRNA 5' ends and expression was assayed in human HeLa cells and BSC-1 and COS-7 monkey cells. In contrast, transcription was totally independent of replication in human 293 cells. These results, which were not due to differences in template copy number, suggest that both cis- and trans-acting factors can influence a promoter's response to DNA replication and point to possible functional similarities between replication origins and transcriptional enhancers.