We have studied the protein-DNA interactions of human papillomavirus types 16 and 18 constitutive enhancer elements using DNasel footprinting experiments with nuclear extracts from four cervical carcinoma cell lines (C33A, HeLa, SiHa, and CaSki) and one fibroblast cell line (143B). Among nine footprints for the HPV 16 enhancer region, six footprints contain nuclear factor 1 (NF1) binding GCCAA motif. In vitro competition experiments suggest that the same factors are shared by all six of these motifs. Two other sequence motifs have consensus sequences for transcription factor AP1. Another sequence motif, for which uv crosslinking studies reveal interaction with four protein molecules, is a strong positive modulator of HPV 16 enhancer function in vivo and shares 100% homology to a sequence motif, GTTTTAA, in the tissue-specific enhancer of the c-mos oncogene. Footprints on the HPV 18 enhancer show five protected regions with homologies to NF1, AP1, and EFII transcription factor binding motifs. One sequence motif of the HPV 18 enhancer has three repeats of a TTTTA sequence contained within the c-mos sequence motif and interacts with at least four different individual polypeptides, as judged by uv crosslinking experiments.
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