THE ENHANCER IN THE LONG CONTROL REGION OF HUMAN PAPILLOMAVIRUS TYPE-16 IS UP-REGULATED BY PEF-1 AND DOWN-REGULATED BY OCT-1

The minimal enhancer in the long control region of human papillomaviru s type 16 regulates cell type and constitutive expression from the pro moter P97. This region contains at least four DNase I footprints (fp4e , fp5e, fp6e, and fp7e). We have shown that fp5e is crucial to enhance r function and have described an apparently novel factor (PEF-1) bindi ng fp5e (S. Cuthill, G. J. Sibbet, and M. S. Campo, Mol. Carcinog, 8:9 6-104, 1993). Further analyses reveal that Oct-1 or an Oct-related fac tor binds fp5e at a site overlapping that of PEF-1. The binding of Oct -1 to fp5e has been demonstrated by electrophoretic mobility shift ass ays, by oligonucleotide competition studies, and by using an Oct-1-spe cific anti-POU serum. The location of the Oct-i site has been confirme d by a panel of mutants across fp5e. Mutations that block PEF-1 bindin g to fp5e also block enhancer/promoter activity of the long control re gion, whereas mutations that block Oct-i binding significantly increas e enhancer/promoter activity. Thus, although both PEF-1 and Oct-1 inte ract with fp5e, they appear to regulate human papillomavirus expressio n in opposite ways.