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The upstream regulatory region of the human papilloma virus‐16 contains an E2 protein‐independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones.
Author(s) -
Gloss B.,
Bernard H. U.,
Seedorf K.,
Klock G.
Publication year - 1987
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1987.tb02708.x
Subject(s) - biology , enhancer , glucocorticoid , regulatory sequence , papillomaviridae , cancer research , virology , microbiology and biotechnology , genetics , regulation of gene expression , gene , endocrinology , cervical cancer , gene expression , cancer
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.