Epithelial specific transcriptional regulation of the bovine papillomavirus 4 promoter by E2.
Bovine papillomavirus 4 (BPV-4) is a mucosal epitheliotropic papillomavirus. It encodes a transcriptional regulator, E2, which acts on the BPV-4 transcriptional control region (the long control region or LCR) to regulate transcription. The distribution of E2 binding sites within the LCR of BPV-4 is identical to that of the human papillomaviruses HPV-16 and HPV-18, indicating that the mechanism of transcriptional control 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 transcriptional 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 suggest that the epithelial specific transcriptional activation of the BPV-4 LCR promoter is mediated by the E2 transactivation domain. Although low to intermediate levels of E2 can activate transcription from the BPV-4 LCR promoter, high levels of E2 result in down-regulation of transcription from this promoter in keratinocytes. Mutation of E2 binding site 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 epitheliotropic papillomavirus LCRs by E2.
Morgan
I M
IM
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, UK. imm2x@udcf.gla.ac.uk
Grindlay
G J
GJ
Campo
M S
MS
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D052697:Bovine papillomavirus 4; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004848:Epithelium / Q000502:physiology; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D015603:Keratinocytes / Q000378:metabolism*; D009928:Organ Specificity; D010159:Palate / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; D014764:Viral Proteins