Abstract
A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.
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Selected References
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- Baldwin A. S., Jr, Sharp P. A. Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc Natl Acad Sci U S A. 1988 Feb;85(3):723–727. doi: 10.1073/pnas.85.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Broudy V. C., Kaushansky K., Harlan J. M., Adamson J. W. Interleukin 1 stimulates human endothelial cells to produce granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. J Immunol. 1987 Jul 15;139(2):464–468. [PubMed] [Google Scholar]
- Broudy V. C., Kaushansky K., Segal G. M., Harlan J. M., Adamson J. W. Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7467–7471. doi: 10.1073/pnas.83.19.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
- 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]
- Cross S. L., Halden N. F., Lenardo M. J., Leonard W. J. Functionally distinct NF-kappa B binding sites in the immunoglobulin kappa and IL-2 receptor alpha chain genes. Science. 1989 Apr 28;244(4903):466–469. doi: 10.1126/science.2497520. [DOI] [PubMed] [Google Scholar]
- 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]
- Ernst T. J., Ritchie A. R., Demetri G. D., Griffin J. D. Regulation of granulocyte- and monocyte-colony stimulating factor mRNA levels in human blood monocytes is mediated primarily at a post-transcriptional level. J Biol Chem. 1989 Apr 5;264(10):5700–5703. [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Gilman M. Z., Wilson R. N., Weinberg R. A. Multiple protein-binding sites in the 5'-flanking region regulate c-fos expression. Mol Cell Biol. 1986 Dec;6(12):4305–4316. doi: 10.1128/mcb.6.12.4305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heike T., Miyatake S., Yoshida M., Arai K., Arai N. Bovine papilloma virus encoded E2 protein activates lymphokine genes through DNA elements, distinct from the consensus motif, in the long control region of its own genome. EMBO J. 1989 May;8(5):1411–1417. doi: 10.1002/j.1460-2075.1989.tb03522.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoyos B., Ballard D. W., Böhnlein E., Siekevitz M., Greene W. C. Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. Science. 1989 Apr 28;244(4903):457–460. doi: 10.1126/science.2497518. [DOI] [PubMed] [Google Scholar]
- 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]
- Kaushansky K. Control of granulocyte-macrophage colony-stimulating factor production in normal endothelial cells by positive and negative regulatory elements. J Immunol. 1989 Oct 15;143(8):2525–2529. [PubMed] [Google Scholar]
- Kaushansky K., Lin N., Adamson J. W. Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation. J Clin Invest. 1988 Jan;81(1):92–97. doi: 10.1172/JCI113316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Koeffler H. P., Gasson J., Ranyard J., Souza L., Shepard M., Munker R. Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor. Blood. 1987 Jul;70(1):55–59. [PubMed] [Google Scholar]
- Koeffler H. P., Gasson J., Tobler A. Transcriptional and posttranscriptional modulation of myeloid colony-stimulating factor expression by tumor necrosis factor and other agents. Mol Cell Biol. 1988 Aug;8(8):3432–3438. doi: 10.1128/mcb.8.8.3432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenardo M. J., Kuang A., Gifford A., Baltimore D. NF-kappa B protein purification from bovine spleen: nucleotide stimulation and binding site specificity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8825–8829. doi: 10.1073/pnas.85.23.8825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lowenthal J. W., Ballard D. W., Böhnlein E., Greene W. C. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331–2335. doi: 10.1073/pnas.86.7.2331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
- 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]
- Miyatake S., Seiki M., Malefijt R. D., Heike T., Fujisawa J., Takebe Y., Nishida J., Shlomai J., Yokota T., Yoshida M. Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40x protein and bovine papilloma virus encoded E2 protein. Nucleic Acids Res. 1988 Jul 25;16(14A):6547–6566. doi: 10.1093/nar/16.14.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyatake S., Seiki M., Yoshida M., Arai K. T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. Mol Cell Biol. 1988 Dec;8(12):5581–5587. doi: 10.1128/mcb.8.12.5581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Nimer S. D., Gasson J. C., Hu K., Smalberg I., Williams J. L., Chen I. S., Rosenblatt J. D. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene. 1989 Jun;4(6):671–676. [PubMed] [Google Scholar]
- Nimer S. D., Morita E. A., Martis M. J., Wachsman W., Gasson J. C. Characterization of the human granulocyte-macrophage colony-stimulating factor promoter region by genetic analysis: correlation with DNase I footprinting. Mol Cell Biol. 1988 May;8(5):1979–1984. doi: 10.1128/mcb.8.5.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oster W., Lindemann A., Horn S., Mertelsmann R., Herrmann F. Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes. Blood. 1987 Nov;70(5):1700–1703. [PubMed] [Google Scholar]
- Seelentag W. K., Mermod J. J., Montesano R., Vassalli P. Additive effects of interleukin 1 and tumour necrosis factor-alpha on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells. EMBO J. 1987 Aug;6(8):2261–2265. doi: 10.1002/j.1460-2075.1987.tb02499.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Tanabe T., Konishi M., Mizuta T., Noma T., Honjo T. Molecular cloning and structure of the human interleukin-5 gene. J Biol Chem. 1987 Dec 5;262(34):16580–16584. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Wu C., Wilson S., Walker B., Dawid I., Paisley T., Zimarino V., Ueda H. Purification and properties of Drosophila heat shock activator protein. Science. 1987 Nov 27;238(4831):1247–1253. doi: 10.1126/science.3685975. [DOI] [PubMed] [Google Scholar]
- Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
- Zhang Y., Lin J. X., Vilcek J. Synthesis of interleukin 6 (interferon-beta 2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP. J Biol Chem. 1988 May 5;263(13):6177–6182. [PubMed] [Google Scholar]