Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain.

The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also activate a wide range of co-transfected promoters without E2P cores to a lower extent. Analysis of multiple E2 mutants in transfected cells revealed that the C-terminal DNA binding E2 domain binds to the E2P cis sequences in the form of pre-existing nuclear dimers. The DNA binding function of E2 was required for specific trans-activation of the E2P elements, as well as for the function of the previously described C-terminal 'short E2' transrepressor. In addition to the C terminus, specific trans-activation also required an intact N-terminal half of the E2 protein. When expressed alone, the N-terminal E2 domain was found to activate heterologous promoters without E2P elements to an extent comparable to wild-type E2, and therefore represents the functional transcription activation domain of the E2 factor. In contrast to other DNA-binding activator proteins described to date, the transcriptional activation by the E2 factor can occur without specific DNA binding. Its mechanism may thus involve protein--protein interactions between common transcription factors and the N-terminal E2 domain which contains amphipathic helix motifs.