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Enhancers are cis-act ing elements that activate transcription in higher eukaryotes independently of their position or orientation relative to the promoter that they activate¹. The mechanisms by which enhancers activate transcription are poorly understood, in part because, with the exception of the glucocorticoid receptor², the proteins that directly interact with enhancers have not been purified, nor have the genes encoding them been cloned^3–5. The upstream regulatory region (URR) that immediately precedes the early genes of the bovine papillomavirus type 1 genome (BPV) has enhancer activity when it is activated by a trans-acting gene product of the BPV E2 open reading frame (ORF) (Fig. 1)⁶. It is not known whether this enhancement represents a direct or indirect effect of E2 on the URR. We have used an E2 peptide expressed in bacteria and a DNA-protein complex immunoprecipitation assay to study E2 …