AN ADENOVIRUS E1A TRANSCRIPTIONAL REPRESSOR DOMAIN FUNCTIONS AS AN ACTIVATOR WHEN TETHERED TO A PROMOTER

The adenovirus E1A protein contains three well conserved regions, desi gnated conserved region (CR) 1, 2 and 3, which are important for the m ultiple activities ascribed to E1A. The CR3 domain constitutes a proto typic transcription activator, consisting of a promoter targeting regi on and a transactivating region. Here we demonstrate the existence of a second transactivating region located within amino acids 28 to 90 (e ssentially the CR1 domain) of the E1A protein. A fusion protein, conta ining the Ga14 DNA binding domain linked to CR1, was as efficient as t he classical CR3 transactivator in activating transcription from a rep orter plasmid containing Gal4 binding sites. However, competition expe riments suggest that Gal/CR1 and Gal/CR3 work through different cellul ar targets. The E1A-243R protein has previously been extensively chara cterized as a repressor of transcription. Here we show that a Ga14 fus ion protein expressing the CR1 domain is indeed sufficient for repress ion of SV40 enhancer activity. Collectively, our results suggest that CR1 functions as an activator if tethered to a promoter and as a repre ssor in the absence of promoter association.