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. 1990 Oct;87(19):7560–7564. doi: 10.1073/pnas.87.19.7560

Sequence-specific DNA binding by glucocorticoid receptor "zinc finger peptides".

T K Archer 1, G L Hager 1, J G Omichinski 1
PMCID: PMC54787  PMID: 2120703

Abstract

Steroid hormone receptors can activate or repress transcription from responsive loci by binding to DNA. We have examined the mechanism of DNA binding by individually synthesizing the putative "zinc finger peptides" from the rat glucocorticoid receptor. Atomic absorption studies show that the peptides will bind zinc on an equimolar basis, and circular dichroism experiments demonstrate a significant alteration in secondary structure in the presence of zinc. The results from a series of experiments establish that metal ion is required for binding to DNA and that the amino-terminal zinc finger shows a significantly greater affinity for glucocorticoid response element-containing DNA over control DNA. These observations indicate that a single synthetic "zinc finger peptide" is able to bind to DNA in a sequence-specific manner.

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Selected References

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

  1. Archer T. K., Tam S. P., Deugau K. V., Deeley R. G. Apolipoprotein C-II mRNA levels in primate liver. Induction by estrogen in the human hepatocarcinoma cell line, HepG2. J Biol Chem. 1985 Feb 10;260(3):1676–1681. [PubMed] [Google Scholar]
  2. Brown D. D., Schlissel M. S. A positive transcription factor controls the differential expression of two 5S RNA genes. Cell. 1985 Oct;42(3):759–767. doi: 10.1016/0092-8674(85)90272-7. [DOI] [PubMed] [Google Scholar]
  3. Cordingley M. G., Hager G. L. Binding of multiple factors to the MMTV promoter in crude and fractionated nuclear extracts. Nucleic Acids Res. 1988 Jan 25;16(2):609–628. doi: 10.1093/nar/16.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Culp J. S., Webster L. C., Friedman D. J., Smith C. L., Huang W. J., Wu F. Y., Rosenberg M., Ricciardi R. P. The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6450–6454. doi: 10.1073/pnas.85.17.6450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Danielsen M., Hinck L., Ringold G. M. Two amino acids within the knuckle of the first zinc finger specify DNA response element activation by the glucocorticoid receptor. Cell. 1989 Jun 30;57(7):1131–1138. doi: 10.1016/0092-8674(89)90050-0. [DOI] [PubMed] [Google Scholar]
  6. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frankel A. D., Berg J. M., Pabo C. O. Metal-dependent folding of a single zinc finger from transcription factor IIIA. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4841–4845. doi: 10.1073/pnas.84.14.4841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Freedman L. P., Luisi B. F., Korszun Z. R., Basavappa R., Sigler P. B., Yamamoto K. R. The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature. 1988 Aug 11;334(6182):543–546. doi: 10.1038/334543a0. [DOI] [PubMed] [Google Scholar]
  9. Giguère V., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Functional domains of the human glucocorticoid receptor. Cell. 1986 Aug 29;46(5):645–652. doi: 10.1016/0092-8674(86)90339-9. [DOI] [PubMed] [Google Scholar]
  10. Godowski P. J., Rusconi S., Miesfeld R., Yamamoto K. R. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement. Nature. 1987 Jan 22;325(6102):365–368. doi: 10.1038/325365a0. [DOI] [PubMed] [Google Scholar]
  11. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  12. Green S., Chambon P. Oestradiol induction of a glucocorticoid-responsive gene by a chimaeric receptor. Nature. 1987 Jan 1;325(6099):75–78. doi: 10.1038/325075a0. [DOI] [PubMed] [Google Scholar]
  13. Green S., Kumar V., Krust A., Walter P., Chambon P. Structural and functional domains of the estrogen receptor. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):751–758. doi: 10.1101/sqb.1986.051.01.088. [DOI] [PubMed] [Google Scholar]
  14. Green S., Kumar V., Theulaz I., Wahli W., Chambon P. The N-terminal DNA-binding 'zinc finger' of the oestrogen and glucocorticoid receptors determines target gene specificity. EMBO J. 1988 Oct;7(10):3037–3044. doi: 10.1002/j.1460-2075.1988.tb03168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hollenberg S. M., Evans R. M. Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell. 1988 Dec 2;55(5):899–906. doi: 10.1016/0092-8674(88)90145-6. [DOI] [PubMed] [Google Scholar]
  16. Hollenberg S. M., Giguere V., Segui P., Evans R. M. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell. 1987 Apr 10;49(1):39–46. doi: 10.1016/0092-8674(87)90753-7. [DOI] [PubMed] [Google Scholar]
  17. Hollenberg S. M., Weinberger C., Ong E. S., Cerelli G., Oro A., Lebo R., Thompson E. B., Rosenfeld M. G., Evans R. M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature. 1985 Dec 19;318(6047):635–641. doi: 10.1038/318635a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Härd T., Kellenbach E., Boelens R., Maler B. A., Dahlman K., Freedman L. P., Carlstedt-Duke J., Yamamoto K. R., Gustafsson J. A., Kaptein R. Solution structure of the glucocorticoid receptor DNA-binding domain. Science. 1990 Jul 13;249(4965):157–160. doi: 10.1126/science.2115209. [DOI] [PubMed] [Google Scholar]
  19. Jameson B. A., Rao P. E., Kong L. I., Hahn B. H., Shaw G. M., Hood L. E., Kent S. B. Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. Science. 1988 Jun 3;240(4857):1335–1339. doi: 10.1126/science.2453925. [DOI] [PubMed] [Google Scholar]
  20. Jeltsch J. M., Krozowski Z., Quirin-Stricker C., Gronemeyer H., Simpson R. J., Garnier J. M., Krust A., Jacob F., Chambon P. Cloning of the chicken progesterone receptor. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5424–5428. doi: 10.1073/pnas.83.15.5424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Klock G., Strähle U., Schütz G. Oestrogen and glucocorticoid responsive elements are closely related but distinct. Nature. 1987 Oct 22;329(6141):734–736. doi: 10.1038/329734a0. [DOI] [PubMed] [Google Scholar]
  23. Kumar V., Green S., Stack G., Berry M., Jin J. R., Chambon P. Functional domains of the human estrogen receptor. Cell. 1987 Dec 24;51(6):941–951. doi: 10.1016/0092-8674(87)90581-2. [DOI] [PubMed] [Google Scholar]
  24. Kumar V., Green S., Staub A., Chambon P. Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor. EMBO J. 1986 Sep;5(9):2231–2236. doi: 10.1002/j.1460-2075.1986.tb04489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mader S., Kumar V., de Verneuil H., Chambon P. Three amino acids of the oestrogen receptor are essential to its ability to distinguish an oestrogen from a glucocorticoid-responsive element. Nature. 1989 Mar 16;338(6212):271–274. doi: 10.1038/338271a0. [DOI] [PubMed] [Google Scholar]
  26. Miesfeld R., Rusconi S., Godowski P. J., Maler B. A., Okret S., Wikström A. C., Gustafsson J. A., Yamamoto K. R. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell. 1986 Aug 1;46(3):389–399. doi: 10.1016/0092-8674(86)90659-8. [DOI] [PubMed] [Google Scholar]
  27. Nowock J., Borgmeyer U., Püschel A. W., Rupp R. A., Sippel A. E. The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer. Nucleic Acids Res. 1985 Mar 25;13(6):2045–2061. doi: 10.1093/nar/13.6.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ponglikitmongkol M., Green S., Chambon P. Genomic organization of the human oestrogen receptor gene. EMBO J. 1988 Nov;7(11):3385–3388. doi: 10.1002/j.1460-2075.1988.tb03211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Párraga G., Horvath S. J., Eisen A., Taylor W. E., Hood L., Young E. T., Klevit R. E. Zinc-dependent structure of a single-finger domain of yeast ADR1. Science. 1988 Sep 16;241(4872):1489–1492. doi: 10.1126/science.3047872. [DOI] [PubMed] [Google Scholar]
  30. Rhodes D., Klug A. An underlying repeat in some transcriptional control sequences corresponding to half a double helical turn of DNA. Cell. 1986 Jul 4;46(1):123–132. doi: 10.1016/0092-8674(86)90866-4. [DOI] [PubMed] [Google Scholar]
  31. Rosenfeld P. J., Kelly T. J. Purification of nuclear factor I by DNA recognition site affinity chromatography. J Biol Chem. 1986 Jan 25;261(3):1398–1408. [PubMed] [Google Scholar]
  32. Rusconi S., Yamamoto K. R. Functional dissection of the hormone and DNA binding activities of the glucocorticoid receptor. EMBO J. 1987 May;6(5):1309–1315. doi: 10.1002/j.1460-2075.1987.tb02369.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schena M., Freedman L. P., Yamamoto K. R. Mutations in the glucocorticoid receptor zinc finger region that distinguish interdigitated DNA binding and transcriptional enhancement activities. Genes Dev. 1989 Oct;3(10):1590–1601. doi: 10.1101/gad.3.10.1590. [DOI] [PubMed] [Google Scholar]
  34. Severne Y., Wieland S., Schaffner W., Rusconi S. Metal binding 'finger' structures in the glucocorticoid receptor defined by site-directed mutagenesis. EMBO J. 1988 Aug;7(8):2503–2508. doi: 10.1002/j.1460-2075.1988.tb03097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Theulaz I., Hipskind R., ten Heggeler-Bordier B., Green S., Kumar V., Chambon P., Wahli W. Expression of human estrogen receptor mutants in Xenopus oocytes: correlation between transcriptional activity and ability to form protein-DNA complexes. EMBO J. 1988 Jun;7(6):1653–1660. doi: 10.1002/j.1460-2075.1988.tb02992.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Umesono K., Evans R. M. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell. 1989 Jun 30;57(7):1139–1146. doi: 10.1016/0092-8674(89)90051-2. [DOI] [PubMed] [Google Scholar]
  37. 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]

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