A key DNA-protein interaction determines the function of the 5'URR enhancer in human papillomavirus type 11

The 5' end of the upstream regulatory region (URR) of human papillomavirus type 11 (HPV-11) has enhancer function and binds cellular proteins. We have determined that one particular motif, a CCNGTNAC pair, is both necessary and sufficient for enhancer activity. This enhancement of expression can be competed in vivo by concatenated double-stranded oligonucleotides, indicating that protein-DNA binding is a requisite for enhancer activity. A 41-kDa protein, present in all epithelial cells assayed, binds to this enhancer motif. The 5'URR fragment functions as an enhancer both in primary keratinocytes from a variety of body sites and in fibroblasts. We conclude that tissue specificity is not a feature of this enhancer, and that the 41-kDa binding protein is ubiquitous. These data provide evidence that the 5'URR enhancer activity is dependent on only a few sequences and perhaps only one protein.