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
. 1988 Feb;85(3):674–678. doi: 10.1073/pnas.85.3.674

Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene.

M F Shannon 1, J R Gamble 1, M A Vadas 1
PMCID: PMC279617  PMID: 3257571

Abstract

The gene for human granulocyte/macrophage colony-stimulating factor (GM-CSF) is expressed in a tissue-specific as well as an activation-dependent manner. The interaction of nuclear proteins with the promoter region of the GM-CSF gene that is likely to be responsible for this pattern of GM-CSF expression was investigated. We show that nuclear proteins interact with DNA fragments from the GM-CSF promoter in a cell-specific manner. A region spanning two cytokine-specific sequences, cytokine 1 (CK-1, 5' GAGATTCCAC 3') and cytokine 2 (CK-2, 5' TCAGGTA 3') bound two nuclear proteins [nuclear factor (NF)-GMa and NF-GMb] from GM-CSF-expressing cells in gel retardation assays. NF-GMb was inducible with phorbol 12-myristate 13-acetate and accompanied induction of GM-CSF message. NF-GMb was absent in cell lines not producing GM-CSF, some of which had other distinct binding proteins. NF-GMa and NF-GMb eluted from a heparin-Sepharose column at 0.3 and 0.6 M KCl, respectively. We hypothesize that the sequences CK-1 and CK-2 bind specific proteins and regulate GM-CSF transcription.

Full text

PDF
677

Images in this article

676Image
on p.676
676Image
on p.676
676Image
on p.676
676Image
on p.676
677Image
on p.677
677Image
on p.677
677Image
on p.677
677Image
on p.677

Selected References

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

  1. Asano S., Riglar C. Colony growth in agar by human melanoma cells. Cancer Res. 1981 Mar;41(3):1199–1204. [PubMed] [Google Scholar]
  2. Campbell H. D., Ymer S., Fung M. C., Young I. G. Cloning and nucleotide sequence of the murine interleukin-3 gene. Eur J Biochem. 1985 Jul 15;150(2):297–304. doi: 10.1111/j.1432-1033.1985.tb09020.x. [DOI] [PubMed] [Google Scholar]
  3. Chan J. Y., Slamon D. J., Nimer S. D., Golde D. W., Gasson J. C. Regulation of expression of human granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8669–8673. doi: 10.1073/pnas.83.22.8669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen I. S., Quan S. G., Golde D. W. Human T-cell leukemia virus type II transforms normal human lymphocytes. Proc Natl Acad Sci U S A. 1983 Nov;80(22):7006–7009. doi: 10.1073/pnas.80.22.7006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Fuse A., Fujita T., Yasumitsu H., Kashima N., Hasegawa K., Taniguchi T. Organization and structure of the mouse interleukin-2 gene. Nucleic Acids Res. 1984 Dec 21;12(24):9323–9331. doi: 10.1093/nar/12.24.9323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gazdar A. F., Carney D. N., Bunn P. A., Russell E. K., Jaffe E. S., Schechter G. P., Guccion J. G. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980 Mar;55(3):409–417. [PubMed] [Google Scholar]
  9. Goodbourn S., Burstein H., Maniatis T. The human beta-interferon gene enhancer is under negative control. Cell. 1986 May 23;45(4):601–610. doi: 10.1016/0092-8674(86)90292-8. [DOI] [PubMed] [Google Scholar]
  10. Holbrook N. J., Smith K. A., Fornace A. J., Jr, Comeau C. M., Wiskocil R. L., Crabtree G. R. T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1634–1638. doi: 10.1073/pnas.81.6.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Huebner K., Isobe M., Croce C. M., Golde D. W., Kaufman S. E., Gasson J. C. The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly. Science. 1985 Dec 13;230(4731):1282–1285. doi: 10.1126/science.2999978. [DOI] [PubMed] [Google Scholar]
  12. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  13. Kelso A., Metcalf D. Characteristics of colony-stimulating factor production by murine T-lymphocyte clones. Exp Hematol. 1985 Jan;13(1):7–15. [PubMed] [Google Scholar]
  14. Landolfi N. F., Capra J. D., Tucker P. W. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature. 1986 Oct 9;323(6088):548–551. doi: 10.1038/323548a0. [DOI] [PubMed] [Google Scholar]
  15. Le Beau M. M., Westbrook C. A., Diaz M. O., Larson R. A., Rowley J. D., Gasson J. C., Golde D. W., Sherr C. J. Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science. 1986 Feb 28;231(4741):984–987. doi: 10.1126/science.3484837. [DOI] [PubMed] [Google Scholar]
  16. Lopez A. F., Williamson D. J., Gamble J. R., Begley C. G., Harlan J. M., Klebanoff S. J., Waltersdorph A., Wong G., Clark S. C., Vadas M. A. Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest. 1986 Nov;78(5):1220–1228. doi: 10.1172/JCI112705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Metcalf D., Begley C. G., Johnson G. R., Nicola N. A., Vadas M. A., Lopez A. F., Williamson D. J., Wong G. G., Clark S. C., Wang E. A. Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1986 Jan;67(1):37–45. [PubMed] [Google Scholar]
  19. Miyatake S., Otsuka T., Yokota T., Lee F., Arai K. Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985 Oct;4(10):2561–2568. doi: 10.1002/j.1460-2075.1985.tb03971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Munker R., Gasson J., Ogawa M., Koeffler H. P. Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor. Nature. 1986 Sep 4;323(6083):79–82. doi: 10.1038/323079a0. [DOI] [PubMed] [Google Scholar]
  21. Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Yamazaki T. The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor. EMBO J. 1986 Mar;5(3):575–581. doi: 10.1002/j.1460-2075.1986.tb04249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rambaldi A., Young D. C., Griffin J. D. Expression of the M-CSF (CSF-1) gene by human monocytes. Blood. 1987 May;69(5):1409–1413. [PubMed] [Google Scholar]
  23. Royer H. D., Reinherz E. L. Multiple nuclear proteins bind upstream sequences in the promotor region of a T-cell receptor beta-chain variable-region gene: evidence for tissue specificity. Proc Natl Acad Sci U S A. 1987 Jan;84(1):232–236. doi: 10.1073/pnas.84.1.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  25. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  26. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  27. Stanley E., Metcalf D., Sobieszczuk P., Gough N. M., Dunn A. R. The structure and expression of the murine gene encoding granulocyte-macrophage colony stimulating factor: evidence for utilisation of alternative promoters. EMBO J. 1985 Oct;4(10):2569–2573. doi: 10.1002/j.1460-2075.1985.tb03972.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  29. Thorens B., Mermod J. J., Vassalli P. Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. Cell. 1987 Feb 27;48(4):671–679. doi: 10.1016/0092-8674(87)90245-5. [DOI] [PubMed] [Google Scholar]
  30. Tsuchiya M., Kaziro Y., Nagata S. The chromosomal gene structure for murine granulocyte colony-stimulating factor. Eur J Biochem. 1987 May 15;165(1):7–12. doi: 10.1111/j.1432-1033.1987.tb11187.x. [DOI] [PubMed] [Google Scholar]
  31. Vadas M. A., Nicola N. A., Metcalf D. Activation of antibody-dependent cell-mediated cytotoxicity of human neutrophils and eosinophils by separate colony-stimulating factors. J Immunol. 1983 Feb;130(2):795–799. [PubMed] [Google Scholar]
  32. Welte K., Platzer E., Lu L., Gabrilove J. L., Levi E., Mertelsmann R., Moore M. A. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526–1530. doi: 10.1073/pnas.82.5.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  34. Zinn K., Maniatis T. Detection of factors that interact with the human beta-interferon regulatory region in vivo by DNAase I footprinting. Cell. 1986 May 23;45(4):611–618. doi: 10.1016/0092-8674(86)90293-x. [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