Multiple cis-active elements in the long control region of bovine papillomavirus type 1 (BPV-1)

A 1.0 kb region of the BPV-1 genome (the long control region, LCR), contains controls for transcription and the origin of replication. Transcription directed by the LCR is activated by the viral encoded E2 protein. To define the essential cis acting elements that are required to control transcription we have constructed a series of deletions throughout the LCR. We have identified three important domains in the LCR, two of which respond to E2. We have analysed the ability of small subcloned regions of the E2 responsive domains to act as enhancers in a heterologous assay system. This has led to the identification of five independent E2 responsive elements. We have shown that a fragment of only 38 base pairs is sufficient to respond to activation by E2. We also present evidence to suggest two types of E2 responsiveness that result in strong or weak activation. Strong response is correlated with the presence of the sequence 5'-ACCG/TNNNC/TCGGTGC-3' whereas weak response is correlated with the presence of a related sequence 5'-ACC(N)6GGT-3'. The contribution of these multiple elements to viral transcription is discussed.