Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 Jul;9(7):3127–3131. doi: 10.1128/mcb.9.7.3127

Independent glucocorticoid induction and repression of two contiguous responsive genes.

J Charron 1, H Richard-Foy 1, D S Berard 1, G L Hager 1, J Drouin 1
PMCID: PMC362787  PMID: 2550796

Abstract

Specific DNA sequence elements which contain binding sites for the glucocorticoid receptor mediate the action of glucocorticoid hormones on gene transcription. In glucocorticoid-inducible genes, these glucocorticoid-responsive elements behave as hormone-inducible enhancers of transcription. We have taken advantage of the bovine papillomavirus (BPV) system to test the stringency of glucocorticoid regulation of transcription. BPV episomes were constructed to contain two hormone-regulated transcription units in close proximity; one transcription unit is under control of a glucocorticoid-inducible promoter (mouse mammary tumor virus) while the other is under control of a glucocorticoid-inhibited promoter (pro-opiomelanocortin). Glucocorticoids independently regulated transcription of the two physically linked transcription units, irrespective of their relative orientation and of their proximity on the BPV episomes. This result contrasts with the so-called position-independent activity of enhancers and suggests that the multicomponent organization of eucaryotic promoters restricts the action of hormone-responsive regulatory elements to a specific transcription unit, thus accounting for the stringency of hormonal regulation observed in vivo.

Full text

PDF
3131

Images in this article

3129Image
on p.3129

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [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. Benyajati C., Worcel A. Isolation, characterization, and structure of the folded interphase genome of Drosophila melanogaster. Cell. 1976 Nov;9(3):393–407. doi: 10.1016/0092-8674(76)90084-2. [DOI] [PubMed] [Google Scholar]
  4. Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
  5. Charron J., Drouin J. Glucocorticoid inhibition of transcription from episomal proopiomelanocortin gene promoter. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8903–8907. doi: 10.1073/pnas.83.23.8903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
  7. Cordingley M. G., Riegel A. T., Hager G. L. Steroid-dependent interaction of transcription factors with the inducible promoter of mouse mammary tumor virus in vivo. Cell. 1987 Jan 30;48(2):261–270. doi: 10.1016/0092-8674(87)90429-6. [DOI] [PubMed] [Google Scholar]
  8. DeFranco D., Yamamoto K. R. Two different factors act separately or together to specify functionally distinct activities at a single transcriptional enhancer. Mol Cell Biol. 1986 Apr;6(4):993–1001. doi: 10.1128/mcb.6.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drouin J., Chamberland M., Charron J., Jeannotte L., Nemer M. Structure of the rat pro-opiomelanocortin (POMC) gene. FEBS Lett. 1985 Nov 25;193(1):54–58. doi: 10.1016/0014-5793(85)80078-8. [DOI] [PubMed] [Google Scholar]
  10. Drouin J., Charron J., Gagner J. P., Jeannotte L., Nemer M., Plante R. K., Wrange O. Pro-opiomelanocortin gene: a model for negative regulation of transcription by glucocorticoids. J Cell Biochem. 1987 Dec;35(4):293–304. doi: 10.1002/jcb.240350404. [DOI] [PubMed] [Google Scholar]
  11. Fromm M., Berg P. Simian virus 40 early- and late-region promoter functions are enhanced by the 72-base-pair repeat inserted at distant locations and inverted orientations. Mol Cell Biol. 1983 Jun;3(6):991–999. doi: 10.1128/mcb.3.6.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gagner J. P., Drouin J. Opposite regulation of pro-opiomelanocortin gene transcription by glucocorticoids and CRH. Mol Cell Endocrinol. 1985 Apr;40(1):25–32. doi: 10.1016/0303-7207(85)90154-6. [DOI] [PubMed] [Google Scholar]
  13. Gasser S. M., Laemmli U. K. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986 Aug 15;46(4):521–530. doi: 10.1016/0092-8674(86)90877-9. [DOI] [PubMed] [Google Scholar]
  14. Hen R., Borrelli E., Sassone-Corsi P., Chambon P. An enhancer element is located 340 base pairs upstream from the adenovirus-2 E1A capsite. Nucleic Acids Res. 1983 Dec 20;11(24):8747–8760. doi: 10.1093/nar/11.24.8747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang A. L., Ostrowski M. C., Berard D., Hager G. L. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus. Cell. 1981 Dec;27(2 Pt 1):245–255. doi: 10.1016/0092-8674(81)90408-6. [DOI] [PubMed] [Google Scholar]
  16. Hynes N., van Ooyen A. J., Kennedy N., Herrlich P., Ponta H., Groner B. Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3637–3641. doi: 10.1073/pnas.80.12.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Kadesch T., Berg P. Effects of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol. 1986 Jul;6(7):2593–2601. doi: 10.1128/mcb.6.7.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  20. Lee F., Mulligan R., Berg P., Ringold G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature. 1981 Nov 19;294(5838):228–232. doi: 10.1038/294228a0. [DOI] [PubMed] [Google Scholar]
  21. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  22. Miksicek R., Heber A., Schmid W., Danesch U., Posseckert G., Beato M., Schütz G. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus. Cell. 1986 Jul 18;46(2):283–290. doi: 10.1016/0092-8674(86)90745-2. [DOI] [PubMed] [Google Scholar]
  23. Moore D. D., Marks A. R., Buckley D. I., Kapler G., Payvar F., Goodman H. M. The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor. Proc Natl Acad Sci U S A. 1985 Feb;82(3):699–702. doi: 10.1073/pnas.82.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Moreau P., Hen R., Wasylyk B., Everett R., Gaub M. P., Chambon P. The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants. Nucleic Acids Res. 1981 Nov 25;9(22):6047–6068. doi: 10.1093/nar/9.22.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ostrowski M. C., Huang A. L., Kessel M., Wolford R. G., Hager G. L. Modulation of enhancer activity by the hormone responsive regulatory element from mouse mammary tumor virus. EMBO J. 1984 Aug;3(8):1891–1899. doi: 10.1002/j.1460-2075.1984.tb02064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ostrowski M. C., Richard-Foy H., Wolford R. G., Berard D. S., Hager G. L. Glucocorticoid regulation of transcription at an amplified, episomal promoter. Mol Cell Biol. 1983 Nov;3(11):2045–2057. doi: 10.1128/mcb.3.11.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Paulson J. R., Laemmli U. K. The structure of histone-depleted metaphase chromosomes. Cell. 1977 Nov;12(3):817–828. doi: 10.1016/0092-8674(77)90280-x. [DOI] [PubMed] [Google Scholar]
  28. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  29. Ponta H., Kennedy N., Skroch P., Hynes N. E., Groner B. Hormonal response region in the mouse mammary tumor virus long terminal repeat can be dissociated from the proviral promoter and has enhancer properties. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1020–1024. doi: 10.1073/pnas.82.4.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Proudfoot N. J. Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature. 1986 Aug 7;322(6079):562–565. doi: 10.1038/322562a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Richard-Foy H., Hager G. L. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 1987 Aug;6(8):2321–2328. doi: 10.1002/j.1460-2075.1987.tb02507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
  34. Slater E. P., Rabenau O., Karin M., Baxter J. D., Beato M. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol Cell Biol. 1985 Nov;5(11):2984–2992. doi: 10.1128/mcb.5.11.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tremblay Y., Tretjakoff I., Peterson A., Antakly T., Zhang C. X., Drouin J. Pituitary-specific expression and glucocorticoid regulation of a proopiomelanocortin fusion gene in transgenic mice. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8890–8894. doi: 10.1073/pnas.85.23.8890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wang X. F., Calame K. The endogenous immunoglobulin heavy chain enhancer can activate tandem VH promoters separated by a large distance. Cell. 1985 Dec;43(3 Pt 2):659–665. doi: 10.1016/0092-8674(85)90238-7. [DOI] [PubMed] [Google Scholar]
  37. Wasylyk B., Wasylyk C., Augereau P., Chambon P. The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements. Cell. 1983 Feb;32(2):503–514. doi: 10.1016/0092-8674(83)90470-1. [DOI] [PubMed] [Google Scholar]
  38. Wasylyk B., Wasylyk C., Chambon P. Short and long range activation by the SV40 enhancer. Nucleic Acids Res. 1984 Jul 25;12(14):5589–5608. doi: 10.1093/nar/12.14.5589. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES