the Ubiquitous Transcription Factors oct-1, NFA, TEF-2, NF1, and AP-1 Participate in Epithelial Cell-Specific Transcription

The enhancer of human papillomavirus type 16 (HPV-16) is considered to be specific for epithelial cells, in particular for cervical carcinoma-derived cell lines. We reexamined this hypothesis with the complete enhancer as well as nonoverlapping subclones and found all clones to be active in epithelial cell lines derived from the epidermis and from carcinomas of the cervix, mammary gland, and colon, but inactive in fibroblast, lymphoma, and embryonal carcinoma cells. Although the virus infects only human mucosal epithelia, enhancer activity was independent of the exact type or of the species of origin of the transfected epithelial cell. In spite of epithelial cell specificity, we found that the activity of the HPV-16 enhancer varied strongly from a cytomegalovirus enhancer and the simian virus 40 enhancer in a cell line-dependent manner. This suggests varying quantitative contributions of enhancer elements rather than regulation by an all-or-none switch. Cell type specificity was maintained by a 91-bp subclone of the 400-bp enhancer. Most of the enhancer activity of this fragment was eliminated by alternative mutations in binding sites for the ubiquitous factors AP-1, nuclear factor 1 (NFl), or TEF-2. These three types of factors bind this 91-bp enhancer without cooperation, although activation appears to be synergistic. Outside the 91-bp fragment, a motif typical for papillomavirus enhancers, namely an octamerlike sequence flanked by an NFl-binding site, contributes to enhancer function, as the activity was strongly reduced upon its deletion. In HPV-16, this motif is bound by the oct-i factor as well a