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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Nov;84(22):7871–7875. doi: 10.1073/pnas.84.22.7871

A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression.

U Strähle 1, G Klock 1, G Schütz 1
PMCID: PMC299431  PMID: 2891134

Abstract

To define the recognition sequence of the glucocorticoid receptor and its relationship with that of the progesterone receptor, oligonucleotides derived from the glucocorticoid response element of the tyrosine aminotransferase gene were tested upstream of a heterologous promoter for their capacity to mediate effects of these two steroids. We show that a 15-base-pair sequence with partial symmetry is sufficient to confer glucocorticoid inducibility on the promoter of the herpes simplex virus thymidine kinase gene. The same 15-base-pair sequence mediates induction by progesterone. Point mutations in the recognition sequence affect inducibility by glucocorticoids and progesterone similarly. Together with the strong conservation of the sequence of the DNA-binding domain of the two receptors, these data suggest that both proteins recognize a sequence that is similar, if not the same.

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Selected References

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  1. Bailly A., Le Page C., Rauch M., Milgrom E. Sequence-specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation. EMBO J. 1986 Dec 1;5(12):3235–3241. doi: 10.1002/j.1460-2075.1986.tb04634.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Becker P. B., Gloss B., Schmid W., Strähle U., Schütz G. In vivo protein-DNA interactions in a glucocorticoid response element require the presence of the hormone. Nature. 1986 Dec 18;324(6098):686–688. doi: 10.1038/324686a0. [DOI] [PubMed] [Google Scholar]
  3. Buetti E., Kühnel B. Distinct sequence elements involved in the glucocorticoid regulation of the mouse mammary tumor virus promoter identified by linker scanning mutagenesis. J Mol Biol. 1986 Aug 5;190(3):379–389. doi: 10.1016/0022-2836(86)90009-4. [DOI] [PubMed] [Google Scholar]
  4. Cato A. C., Geisse S., Wenz M., Westphal H. M., Beato M. The nucleotide sequences recognized by the glucocorticoid receptor in the rabbit uteroglobin gene region are located far upstream from the initiation of transcription. EMBO J. 1984 Dec 1;3(12):2771–2778. doi: 10.1002/j.1460-2075.1984.tb02208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cato A. C., Miksicek R., Schütz G., Arnemann J., Beato M. The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction. EMBO J. 1986 Sep;5(9):2237–2240. doi: 10.1002/j.1460-2075.1986.tb04490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Green S., Chambon P. A superfamily of potentially oncogenic hormone receptors. Nature. 1986 Dec 18;324(6098):615–617. doi: 10.1038/324615a0. [DOI] [PubMed] [Google Scholar]
  9. Herrmann W., Wyss R., Riondel A., Philibert D., Teutsch G., Sakiz E., Baulieu E. E. Effet d'un stéroide anti-progestérone chez la femme: interruption du cycle menstruel et de la grossesse au début. C R Seances Acad Sci III. 1982 May 17;294(18):933–938. [PubMed] [Google Scholar]
  10. Horwitz K. B., Zava D. T., Thilagar A. K., Jensen E. M., McGuire W. L. Steroid receptor analyses of nine human breast cancer cell lines. Cancer Res. 1978 Aug;38(8):2434–2437. [PubMed] [Google Scholar]
  11. Jantzen H. M., Strähle U., Gloss B., Stewart F., Schmid W., Boshart M., Miksicek R., Schütz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987 Apr 10;49(1):29–38. doi: 10.1016/0092-8674(87)90752-5. [DOI] [PubMed] [Google Scholar]
  12. Klein-Hitpass L., Schorpp M., Wagner U., Ryffel G. U. An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 1986 Sep 26;46(7):1053–1061. doi: 10.1016/0092-8674(86)90705-1. [DOI] [PubMed] [Google Scholar]
  13. Kühnel B., Buetti E., Diggelmann H. Functional analysis of the glucocorticoid regulatory elements present in the mouse mammary tumor virus long terminal repeat. A synthetic distal binding site can replace the proximal binding domain. J Mol Biol. 1986 Aug 5;190(3):367–378. doi: 10.1016/0022-2836(86)90008-2. [DOI] [PubMed] [Google Scholar]
  14. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moguilewsky M., Philibert D. RU 38486: potent antiglucocorticoid activity correlated with strong binding to the cytosolic glucocorticoid receptor followed by an impaired activation. J Steroid Biochem. 1984 Jan;20(1):271–276. doi: 10.1016/0022-4731(84)90216-4. [DOI] [PubMed] [Google Scholar]
  16. Renkawitz R., Schütz G., von der Ahe D., Beato M. Sequences in the promoter region of the chicken lysozyme gene required for steroid regulation and receptor binding. Cell. 1984 Jun;37(2):503–510. doi: 10.1016/0092-8674(84)90380-5. [DOI] [PubMed] [Google Scholar]
  17. Ringold G. M. Steroid hormone regulation of gene expression. Annu Rev Pharmacol Toxicol. 1985;25:529–566. doi: 10.1146/annurev.pa.25.040185.002525. [DOI] [PubMed] [Google Scholar]
  18. Scheidereit C., Westphal H. M., Carlson C., Bosshard H., Beato M. Molecular model of the interaction between the glucocorticoid receptor and the regulatory elements of inducible genes. DNA. 1986 Oct;5(5):383–391. doi: 10.1089/dna.1986.5.383. [DOI] [PubMed] [Google Scholar]
  19. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  20. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
  21. von der Ahe D., Janich S., Scheidereit C., Renkawitz R., Schütz G., Beato M. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. Nature. 1985 Feb 21;313(6004):706–709. doi: 10.1038/313706a0. [DOI] [PubMed] [Google Scholar]
  22. von der Ahe D., Renoir J. M., Buchou T., Baulieu E. E., Beato M. Receptors for glucocorticosteroid and progesterone recognize distinct features of a DNA regulatory element. Proc Natl Acad Sci U S A. 1986 May;83(9):2817–2821. doi: 10.1073/pnas.83.9.2817. [DOI] [PMC free article] [PubMed] [Google Scholar]

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