Positive and negative E2-independent regulatory elements in the long control region of bovine papillomavirus type 4

Abstract

The long control region (LCR) of bovine papillomavirus type 4 demonstrated enhancer activity when cloned upstream of a bacterial chloramphenicol acetyltransferase reporter gene under thymidine kinase promoter control. Deletion analysis of the LCR revealed the presence of several positive and negative control elements, all of which could function independently of the viral E2 trans-activator. Each of the three positive elements present appeared to be paired with a negative element which modulated its activity. DNase I footprinting was used to identify protein binding sites within the LCR, which might represent these control elements. The results suggest a highly complex and finely tuned control of viral gene expression.

Detection of silencer activity in the long control regions of human papillomavirus type 6 isolated from both benign and malignant lesions

“…Consistent with this hypothesis, both HPV6-T70 and HPV6-W50 contain the ACTGT sequence. However, it should be noted that the sequence AAGTGTTG, comparable to that of HPV-6e, was found to have silencing activity when present in the bovine papillomavirus type 4 genome (Jackson & Campo, 1991). Thus the context of the sequence may be important.…”

A Novel Silencer Element in the Bovine Papillomavirus Type 4 Promoter Represses the Transcriptional Response to Papillomavirus E2 Protein

“…The BPV-4 promoter used does not have the putative initiator element identified in the BPV-4 LCR (8) or contain any potential binding sites for cellular factors commonly found in papillomavirus promoters (18). The results presented here demonstrate that the upstream BPV-4 promoter region contains two novel repressor elements that are, at least in part, responsible for mediating the differential response of this promoter to upstream activators in fibroblasts and keratinocytes.…”

The bovine papillomavirus type 4 long control region contains an epithelial specific enhancer.

“…This suggests that BPV-4 uses a different combination of cellular factors from HPV-16 and -18 to control transcription from the LCR promoter. Previous studies have shown that the LCR of BPV-4 contains negative and positive control elements that regulate transcription from the TK promoter (Jackson & Campo, 1991). However, it is not known whether the transcriptional control elements of this viral LCR are epithelial specific.…”

“…As mentioned above, the transcription factor family C\EBP has been implicated as both a positive and negative regulator of transcription from HPV and BPV-4 LCRs (Bauknecht et al, 1996 ;Bauknecht & Shi, 1998 ;McCaffery & Jackson, 1994 ;Wang et al, 1996). Also, there are several putative binding sites for the NF1 transcription factor family in the BPV-4 LCR (Jackson & Campo, 1991). It has been well documented that this family is involved in regulating transcription from HPV LCRs (Apt et al, 1993(Apt et al, , 1994O'Connor & Bernard, 1995).…”

“…Here, we have demonstrated that the BPV-4 LCR has an epithelial specific enhancer that has two main regions contributing towards this enhancer activity. Footprinting studies have demonstrated that cellular factors bind to these two regions (Jackson & Campo, 1991). One of the sites, Site2, has a corresponding sequence in the LCR promoter region of HPV-16.…”