Skip to main content
PMC home page
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
. 1990 Jul;87(13):5046–5050. doi: 10.1073/pnas.87.13.5046

Positive and negative elements regulate human interleukin 3 expression.

B Mathey-Prevot 1, N C Andrews 1, H S Murphy 1, S G Kreissman 1, D G Nathan 1
PMCID: PMC54258  PMID: 1695008

Abstract

The human interleukin 3 (IL-3) promoter is comprised of several cis-acting DNA sequences that modulate T-cell expression of IL-3. These are located within 315 nucleotides upstream of the mRNA start site. Transient expression of reporter genes linked to serially deleted sequences of the IL-3 promoter has allowed mapping of two activator sequences and an interposed repressor sequence. The proximal regulatory region is specific to IL-3 and prerequisite for efficient transcription. Its effect is enhanced by a second, more distal activating sequence consisting of an AP-1 binding site. Between the two activators lies a transcriptional silencer, which is a potent repressor in the absence of the AP-1 site. DNA-nuclear protein binding experiments demonstrate specific complex formation within each of these functional regions. Thus, both positive and negative regulatory elements appear to control expression of the human IL-3 gene in activated T cells.

Full text

PDF
5046

Images in this article

5047Image
on p.5047
5048Image
on p.5048
5048Image
on p.5048
5049Image
on p.5049
5049Image
on p.5049
5049Image
on p.5049

Selected References

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

  1. Alcover A., Ramarli D., Richardson N. E., Chang H. C., Reinherz E. L. Functional and molecular aspects of human T lymphocyte activation via T3-Ti and T11 pathways. Immunol Rev. 1987 Feb;95:5–36. doi: 10.1111/j.1600-065x.1987.tb00498.x. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  3. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  4. Curran T., Franza B. R., Jr Fos and Jun: the AP-1 connection. Cell. 1988 Nov 4;55(3):395–397. doi: 10.1016/0092-8674(88)90024-4. [DOI] [PubMed] [Google Scholar]
  5. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Emmel E. A., Verweij C. L., Durand D. B., Higgins K. M., Lacy E., Crabtree G. R. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science. 1989 Dec 22;246(4937):1617–1620. doi: 10.1126/science.2595372. [DOI] [PubMed] [Google Scholar]
  7. Fujita T., Takaoka C., Matsui H., Taniguchi T. Structure of the human interleukin 2 gene. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7437–7441. doi: 10.1073/pnas.80.24.7437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gelfand E. W., Mills G. B., Cheung R. K., Lee J. W., Grinstein S. Transmembrane ion fluxes during activation of human T lymphocytes: role of Ca2+, Na+/H+ exchange and phospholipid turnover. Immunol Rev. 1987 Feb;95:59–87. doi: 10.1111/j.1600-065x.1987.tb00500.x. [DOI] [PubMed] [Google Scholar]
  9. Kawakami T. G., Huff S. D., Buckley P. M., Dungworth D. L., Synder S. P., Gilden R. V. C-type virus associated with gibbon lymphosarcoma. Nat New Biol. 1972 Feb 9;235(58):170–171. doi: 10.1038/newbio235170a0. [DOI] [PubMed] [Google Scholar]
  10. Levine M., Manley J. L. Transcriptional repression of eukaryotic promoters. Cell. 1989 Nov 3;59(3):405–408. doi: 10.1016/0092-8674(89)90024-x. [DOI] [PubMed] [Google Scholar]
  11. Martin D. I., Tsai S. F., Orkin S. H. Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor. Nature. 1989 Mar 30;338(6214):435–438. doi: 10.1038/338435a0. [DOI] [PubMed] [Google Scholar]
  12. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Niemeyer C. M., Sieff C. A., Mathey-Prevot B., Wimperis J. Z., Bierer B. E., Clark S. C., Nathan D. G. Expression of human interleukin-3 (multi-CSF) is restricted to human lymphocytes and T-cell tumor lines. Blood. 1989 Mar;73(4):945–951. [PubMed] [Google Scholar]
  14. Otsuka T., Miyajima A., Brown N., Otsu K., Abrams J., Saeland S., Caux C., de Waal Malefijt R., de Vries J., Meyerson P. Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones. J Immunol. 1988 Apr 1;140(7):2288–2295. [PubMed] [Google Scholar]
  15. Shannon M. F., Gamble J. R., Vadas M. A. Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene. Proc Natl Acad Sci U S A. 1988 Feb;85(3):674–678. doi: 10.1073/pnas.85.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sieff C. A. Hematopoietic growth factors. J Clin Invest. 1987 Jun;79(6):1549–1557. doi: 10.1172/JCI112988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yang Y. C., Kovacic S., Kriz R., Wolf S., Clark S. C., Wellems T. E., Nienhuis A., Epstein N. The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. Blood. 1988 Apr;71(4):958–961. [PubMed] [Google Scholar]
  18. 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]

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