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.