Co-operative interaction between the initiator E1 and the transcriptional activator E2 is required for replicator specific DNA replication of bovine papillomavirus in vivo and in vitro

The E1 polypeptide from bovine papillomavirus binds to the origin of replication (ori) and possesses the activities attributed to initiator proteins. E1 is also the only viral protein required for replication in a cell-free replication system, Replication in vivo, however, absolutely requires in addition the viral transcription factor E2. We demonstrate that the basis for this distinction between in vitro and in vivo requirements is the limited sequence specificity of the E1 protein. E1 and E2, which bind the ori individually with low sequence specificity, together bind with greatly increased sequence specificity. This combinatorial effect provides a function for the involvement of transcriptional activation domains in replication and suggests common mechanisms of action for transcription factors in both transcription and replication. It also provides a possible explanation for the differential specificity that is observed for auxiliary transcription factors in vivo.