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. 1991 Dec 11;19(23):6527–6532. doi: 10.1093/nar/19.23.6527

H-DNA and Z-DNA in the mouse c-Ki-ras promoter.

D G Pestov 1, A Dayn 1, Siyanova EYu 1, D L George 1, S M Mirkin 1
PMCID: PMC329212  PMID: 1754390

Abstract

The mouse c-Ki-ras protooncogene promoter contains a homopurine-homopyrimidine domain that exhibits S1 nuclease sensitivity in vitro. We have studied the structure of this DNA region in a supercoiled state using a number of chemical probes for non-B DNA conformations including diethyl pyrocarbonate, osmium tetroxide, chloroacetaldehyde, and dimethyl sulfate. The results demonstrate that two types of unusual DNA structures formed under different environmental conditions. A 27-bp homopurine-homopyrimidine mirror repeat adopts a triple-helical H-DNA conformation under mildly acidic conditions. This H-DNA seems to account for the S1 hypersensitivity of the promoter in vitro, since the observed pattern of S1 hypersensitivity at a single base level fits well with the H-DNA formation. Under conditions of neutral pH we have detected Z-DNA created by a (CG)5-stretch, located adjacent to the homopurine-homopyrimidine mirror repeat. The ability of the promoter DNA segment to form non-B structures has implications for models of gene regulation.

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Selected References

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

  1. Anshelevich V. V., Vologodskii A. V., Frank-Kamenetskii M. D. A theoretical study of formation of DNA noncanonical structures under negative superhelical stress. J Biomol Struct Dyn. 1988 Oct;6(2):247–259. doi: 10.1080/07391102.1988.10507711. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  3. Caddle M. S., Lussier R. H., Heintz N. H. Intramolecular DNA triplexes, bent DNA and DNA unwinding elements in the initiation region of an amplified dihydrofolate reductase replicon. J Mol Biol. 1990 Jan 5;211(1):19–33. doi: 10.1016/0022-2836(90)90008-A. [DOI] [PubMed] [Google Scholar]
  4. Clark S. P., Lewis C. D., Felsenfeld G. Properties of BGP1, a poly(dG)-binding protein from chicken erythrocytes. Nucleic Acids Res. 1990 Sep 11;18(17):5119–5126. doi: 10.1093/nar/18.17.5119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooney M., Czernuszewicz G., Postel E. H., Flint S. J., Hogan M. E. Site-specific oligonucleotide binding represses transcription of the human c-myc gene in vitro. Science. 1988 Jul 22;241(4864):456–459. doi: 10.1126/science.3293213. [DOI] [PubMed] [Google Scholar]
  6. Galazka G., Palecek E., Wells R. D., Klysik J. Site-specific OsO4 modification of the B-Z junctions formed at the (dA-dC)32 region in supercoiled DNA. J Biol Chem. 1986 May 25;261(15):7093–7098. [PubMed] [Google Scholar]
  7. Gilmour D. S., Thomas G. H., Elgin S. C. Drosophila nuclear proteins bind to regions of alternating C and T residues in gene promoters. Science. 1989 Sep 29;245(4925):1487–1490. doi: 10.1126/science.2781290. [DOI] [PubMed] [Google Scholar]
  8. Glaser R. L., Thomas G. H., Siegfried E., Elgin S. C., Lis J. T. Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. J Mol Biol. 1990 Feb 20;211(4):751–761. doi: 10.1016/0022-2836(90)90075-W. [DOI] [PubMed] [Google Scholar]
  9. Hanvey J. C., Klysik J., Wells R. D. Influence of DNA sequence on the formation of non-B right-handed helices in oligopurine.oligopyrimidine inserts in plasmids. J Biol Chem. 1988 May 25;263(15):7386–7396. [PubMed] [Google Scholar]
  10. Herr W. Diethyl pyrocarbonate: a chemical probe for secondary structure in negatively supercoiled DNA. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8009–8013. doi: 10.1073/pnas.82.23.8009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoffman E. K., Trusko S. P., Murphy M., George D. L. An S1 nuclease-sensitive homopurine/homopyrimidine domain in the c-Ki-ras promoter interacts with a nuclear factor. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2705–2709. doi: 10.1073/pnas.87.7.2705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Htun H., Dahlberg J. E. Single strands, triple strands, and kinks in H-DNA. Science. 1988 Sep 30;241(4874):1791–1796. doi: 10.1126/science.3175620. [DOI] [PubMed] [Google Scholar]
  13. Htun H., Dahlberg J. E. Topology and formation of triple-stranded H-DNA. Science. 1989 Mar 24;243(4898):1571–1576. doi: 10.1126/science.2648571. [DOI] [PubMed] [Google Scholar]
  14. Johnson A. C., Jinno Y., Merlino G. T. Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. Mol Cell Biol. 1988 Oct;8(10):4174–4184. doi: 10.1128/mcb.8.10.4174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnston B. H., Rich A. Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution. Cell. 1985 Oct;42(3):713–724. doi: 10.1016/0092-8674(85)90268-5. [DOI] [PubMed] [Google Scholar]
  16. Johnston B. H. The S1-sensitive form of d(C-T)n.d(A-G)n: chemical evidence for a three-stranded structure in plasmids. Science. 1988 Sep 30;241(4874):1800–1804. doi: 10.1126/science.2845572. [DOI] [PubMed] [Google Scholar]
  17. Kang D. S., Wells R. D. B-Z DNA junctions contain few, if any, nonpaired bases at physiological superhelical densities. J Biol Chem. 1985 Jun 25;260(12):7783–7790. [PubMed] [Google Scholar]
  18. Kinniburgh A. J. A cis-acting transcription element of the c-myc gene can assume an H-DNA conformation. Nucleic Acids Res. 1989 Oct 11;17(19):7771–7778. doi: 10.1093/nar/17.19.7771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kohwi-Shigematsu T., Manes T., Kohwi Y. Unusual conformational effect exerted by Z-DNA upon its neighboring sequences. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2223–2227. doi: 10.1073/pnas.84.8.2223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kohwi Y. Cationic metal-specific structures adopted by the poly(dG) region and the direct repeats in the chicken adult beta A globin gene promoter. Nucleic Acids Res. 1989 Jun 26;17(12):4493–4502. doi: 10.1093/nar/17.12.4493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kohwi Y., Kohwi-Shigematsu T. Magnesium ion-dependent triple-helix structure formed by homopurine-homopyrimidine sequences in supercoiled plasmid DNA. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3781–3785. doi: 10.1073/pnas.85.11.3781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Larsen A., Weintraub H. An altered DNA conformation detected by S1 nuclease occurs at specific regions in active chick globin chromatin. Cell. 1982 Jun;29(2):609–622. doi: 10.1016/0092-8674(82)90177-5. [DOI] [PubMed] [Google Scholar]
  23. Lyamichev V. I., Mirkin S. M., Frank-Kamenetskii M. D. A pH-dependent structural transition in the homopurine-homopyrimidine tract in superhelical DNA. J Biomol Struct Dyn. 1985 Oct;3(2):327–338. doi: 10.1080/07391102.1985.10508420. [DOI] [PubMed] [Google Scholar]
  24. Lyamichev V. I., Mirkin S. M., Frank-Kamenetskii M. D. Structures of homopurine-homopyrimidine tract in superhelical DNA. J Biomol Struct Dyn. 1986 Feb;3(4):667–669. doi: 10.1080/07391102.1986.10508454. [DOI] [PubMed] [Google Scholar]
  25. Mavrothalassitis G. J., Watson D. K., Papas T. S. Molecular and functional characterization of the promoter of ETS2, the human c-ets-2 gene. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1047–1051. doi: 10.1073/pnas.87.3.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  27. McKeon C., Schmidt A., de Crombrugghe B. A sequence conserved in both the chicken and mouse alpha 2(I) collagen promoter contains sites sensitive to S1 nuclease. J Biol Chem. 1984 May 25;259(10):6636–6640. [PubMed] [Google Scholar]
  28. Mirkin S. M., Lyamichev V. I., Drushlyak K. N., Dobrynin V. N., Filippov S. A., Frank-Kamenetskii M. D. DNA H form requires a homopurine-homopyrimidine mirror repeat. Nature. 1987 Dec 3;330(6147):495–497. doi: 10.1038/330495a0. [DOI] [PubMed] [Google Scholar]
  29. Mirkin S. M., Lyamichev V. I., Kumarev V. P., Kobzev V. F., Nosikov V. V., Vologodskii A. V. The energetics of the B-Z transition in DNA. J Biomol Struct Dyn. 1987 Aug;5(1):79–88. doi: 10.1080/07391102.1987.10506376. [DOI] [PubMed] [Google Scholar]
  30. Postel E. H., Mango S. E., Flint S. J. A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor. Mol Cell Biol. 1989 Nov;9(11):5123–5133. doi: 10.1128/mcb.9.11.5123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rahmouni A. R., Wells R. D. Stabilization of Z DNA in vivo by localized supercoiling. Science. 1989 Oct 20;246(4928):358–363. doi: 10.1126/science.2678475. [DOI] [PubMed] [Google Scholar]
  32. Singleton C. K., Klysik J., Stirdivant S. M., Wells R. D. Left-handed Z-DNA is induced by supercoiling in physiological ionic conditions. Nature. 1982 Sep 23;299(5881):312–316. doi: 10.1038/299312a0. [DOI] [PubMed] [Google Scholar]
  33. Vojtísková M., Mirkin S., Lyamichev V., Voloshin O., Frank-Kamenetskii M., Palecek E. Chemical probing of the homopurine.homopyrimidine tract in supercoiled DNA at single-nucleotide resolution. FEBS Lett. 1988 Jul 18;234(2):295–299. doi: 10.1016/0014-5793(88)80102-9. [DOI] [PubMed] [Google Scholar]
  34. Voloshin O. N., Mirkin S. M., Lyamichev V. I., Belotserkovskii B. P., Frank-Kamenetskii M. D. Chemical probing of homopurine-homopyrimidine mirror repeats in supercoiled DNA. Nature. 1988 Jun 2;333(6172):475–476. doi: 10.1038/333475a0. [DOI] [PubMed] [Google Scholar]
  35. Weinreb A., Collier D. A., Birshtein B. K., Wells R. D. Left-handed Z-DNA and intramolecular triplex formation at the site of an unequal sister chromatid exchange. J Biol Chem. 1990 Jan 25;265(3):1352–1359. [PubMed] [Google Scholar]
  36. Weintraub H. A dominant role for DNA secondary structure in forming hypersensitive structures in chromatin. Cell. 1983 Apr;32(4):1191–1203. doi: 10.1016/0092-8674(83)90302-1. [DOI] [PubMed] [Google Scholar]
  37. Wells R. D., Collier D. A., Hanvey J. C., Shimizu M., Wohlrab F. The chemistry and biology of unusual DNA structures adopted by oligopurine.oligopyrimidine sequences. FASEB J. 1988 Nov;2(14):2939–2949. [PubMed] [Google Scholar]
  38. Yavachev L. P., Georgiev O. I., Braga E. A., Avdonina T. A., Bogomolova A. E., Zhurkin V. B., Nosikov V. V., Hadjiolov A. A. Nucleotide sequence analysis of the spacer regions flanking the rat rRNA transcription unit and identification of repetitive elements. Nucleic Acids Res. 1986 Mar 25;14(6):2799–2810. doi: 10.1093/nar/14.6.2799. [DOI] [PMC free article] [PubMed] [Google Scholar]

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