EPITHELIAL SPECIFIC TRANSCRIPTIONAL REGULATION OF THE BOVINE PAPILLOMAVIRUS-4 PROMOTER BY E2

Bovine papillomavirus 4 (BPV-4) is a mucosal epitheliotropic papilloma virus, It encodes a transcriptional regulator, E2, which acts on the B PV-4 transcriptional control region (the long control region or LCR) t o regulate transcription, The distribution of E2 binding sites within the LCR of BPV-4 is identical to that of the human papillomaviruses HP V-16 and HPV-18, indicating that the mechanism of transcriptional cont rol by E2 of mucosal epitheliotropic papillomaviruses is conserved, In this study it has been shown that E2 activates transcription through the BPV-4 LCR promoter in primary bovine palate keratinocytes but not in primary bovine palate fibroblasts, The epithelial specific transcri ptional activation of the BPV-4 LCR by E2 is promoter-specific because following binding to the BPV-4 LCR placed in an enhancer mode, E2 can activate transcription from heterologous promoters, such as SV40, in both keratinocytes and fibroblasts, Chimaeric VP16-E2 molecules sugges t that the epithelial specific transcriptional activation of the BPV-4 LCR promoter is mediated by the E2 transactivation domain, Although l ow to intermediate levels of E2 can activate transcription from the BP V-4 LCR promoter, high levels of E2 result in down-regulation of trans cription from this promoter in keratinocytes. Mutation of E2 binding s ite 1 (BS1), which is 3 bp upstream from the TATA box, abrogates down- regulation of transcription by high levels of E2, The results present a model system for studying transcriptional regulation of mucosal epit heliotropic papillomavirus LCRs by E2.