The upstream regulatory region of the human papilloma virus‐16 (HPV‐16) genomic DNA contains a sequence element with a large degree of homology to the partially palindromic sequence GGTACANNNTGTTCT, which is the consensus sequence of the glucocorticoid responsive elements of known genes regulated by this steroid hormone. DNase I and dimethylsulfate protection experiments reveal the binding of this sequence by rat glucocorticoid receptor protein. A 400‐bp DNA segment centrally containing this sequence confers strong inducibility by dexamethasone to the promoter p97 of HPV‐16 and to the Herpes simplex virus thymidine kinase promoter, as judged by chloramphenicol acetyltransferase activity and RNase protection assays. The same DNA segment, that does not contain the consensus sequences of all papilloma viruses relevant for E2 protein‐mediated transcription enhancement, functions in an enhancer‐like fashion in addition to its glucocorticoid responsive action. This hormone‐independent transcription enhancement is absent in human MCF7 cells, but is strong in human HeLa cells where the combined activity of the constitutive and the steroid hormone‐dependent enhancer elements stimulate transcription by a factor of 500. This cell type specificity of the HPV‐16 enhancer may be responsible for the tissue tropism of the virus. These observations and the presence of numerous homologies to known enhancers of cellular and viral genes suggest a complex pattern of activation of the human papilloma virus‐16 promoters.

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DNA sequences recognized by the glucocorticoid receptor are termed glucocorticoid-responsive elements because of their stimulatory effect on transcription. An oligonucleotide of 15 base pairs having partial or perfect symmetry is necessary for glucocorticoid induction and this same oligonucleotide is surprisingly also recognized by the progesterone receptor. Here we define a palindromic sequence of 15 base pairs, modelled after a sequence element shared by the vitellogenin genes of frog and chicken, which confers oestrogen inducibility on a heterologous promoter and can be converted into a glucocorticoid-responsive element by substitution of one or two bases at homologous positions in the palindrome. Considered with the observation that the DNA-binding domains of steroid receptors are closely related, this finding demonstrates that the steroid-responsive elements constitute a family of related DNA sequences.