Upstream DNA sequences determine different autoregulatory responses of the adenovirus types 5 and 3 E1A promoters

Adenovirus types 5 and 3 (Ad5 and Ad3), two human adenovirus serotypes of evolutionarily divergent subgroups, show very different levels of E1A gene expression early after infection of permissive cells. Since adenovirus E1A gene expression is known to be transcriptionally autoregulated, we have investigated the difference between Ad3 and Ad5 by monitoring transient expression of a reporter gene under transcriptional control of the E1A promoter of Ad5 or Ad3. There was only a modest difference between the basal levels of transcription driven by these two E1A promoters. This difference was amplified from 10 to 100 times by the different net responses of the E1A promoters to concomitantly expressed E1A genes. Each promoter had a characteristic net response to positive and negative regulation by E1A gene products. The Ad5 E1A promoter was more strongly repressed, whereas the Ad3 E1A promoter was more strongly activated by E1A gene products. Experiments with a chimeric Ad5/3 E1A promoter indicated that these different autoregulatory responses are determined by DNA sequences which are more than 50 base pairs upstream from the E1A transcriptional start site. A plausible target DNA sequence for positive and negative autoregulation by E1A gene products is discussed.