Skip to main content
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
. 1991 Jan 15;88(2):666–670. doi: 10.1073/pnas.88.2.666

Hairpin formation within the enhancer region of the human enkephalin gene.

C T McMurray 1, W D Wilson 1, J O Douglass 1
PMCID: PMC50873  PMID: 1988963

Abstract

The 3',5'-cyclic adenosine monophosphate (cAMP)-inducible enhancer of the human enkephalin gene is located within an imperfect palindrome of 23 base pairs. We have found that a 23-base-pair oligonucleotide duplex containing the enhancer undergoes a reversible conformational transition from the duplex to two individual hairpin structures each formed from one strand of the duplex. Each individual hairpin forms with mismatched base pairs, one containing two GT pairs and the other containing two AC pairs. The conformational transition is stabilized by proton transfer to the hairpin containing AC mismatched pairs. The unique physical and thermodynamic properties of the enkephalin enhancer DNA suggest a model in which DNA secondary structure within the enhancer region plays an active role in cAMP-inducible activation of the human enkephalin gene via formation of cruciform structures.

Full text

PDF
666

Images in this article

Selected References

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

  1. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  2. Comb M., Birnberg N. C., Seasholtz A., Herbert E., Goodman H. M. A cyclic AMP- and phorbol ester-inducible DNA element. 1986 Sep 25-Oct 1Nature. 323(6086):353–356. doi: 10.1038/323353a0. [DOI] [PubMed] [Google Scholar]
  3. Comb M., Mermod N., Hyman S. E., Pearlberg J., Ross M. E., Goodman H. M. Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription. EMBO J. 1988 Dec 1;7(12):3793–3805. doi: 10.1002/j.1460-2075.1988.tb03264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hyman S. E., Comb M., Pearlberg J., Goodman H. M. An AP-2 element acts synergistically with the cyclic AMP- and phorbol ester-inducible enhancer of the human proenkephalin gene. Mol Cell Biol. 1989 Jan;9(1):321–324. doi: 10.1128/mcb.9.1.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Marky L. A., Breslauer K. J. Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopolymers. 1987 Sep;26(9):1601–1620. doi: 10.1002/bip.360260911. [DOI] [PubMed] [Google Scholar]
  6. Record M. T., Jr, Anderson C. F., Lohman T. M. Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity. Q Rev Biophys. 1978 May;11(2):103–178. doi: 10.1017/s003358350000202x. [DOI] [PubMed] [Google Scholar]
  7. Sanger F., Coulson A. R. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975 May 25;94(3):441–448. doi: 10.1016/0022-2836(75)90213-2. [DOI] [PubMed] [Google Scholar]
  8. Sonnenberg J. L., Rauscher F. J., 3rd, Morgan J. I., Curran T. Regulation of proenkephalin by Fos and Jun. Science. 1989 Dec 22;246(4937):1622–1625. doi: 10.1126/science.2512642. [DOI] [PubMed] [Google Scholar]
  9. Struhl K. The DNA-binding domains of the jun oncoprotein and the yeast GCN4 transcriptional activator protein are functionally homologous. Cell. 1987 Sep 11;50(6):841–846. doi: 10.1016/0092-8674(87)90511-3. [DOI] [PubMed] [Google Scholar]
  10. Wilson W. D., Zuo E. T., Jones R. L., Zon G. L., Baumstark B. R. Sequence dependent electrophoretic mobilities and melting temperatures for A-T containing oligodeoxyribonucleotides. Nucleic Acids Res. 1987 Jan 12;15(1):105–118. doi: 10.1093/nar/15.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES