Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1993 Apr;13(4):2141–2151. doi: 10.1128/mcb.13.4.2141

The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1).

J Suzow 1, A D Friedman 1
PMCID: PMC359535  PMID: 8384306

Abstract

The myeloperoxidase (MPO) gene is expressed specifically in myeloid cells. There is significant homology between the murine and human MPO genes in the 1.6-kb region located upstream of the murine MPO transcription initiation sites. 5',3', and internal deletions of this DNA segment localized several cis-acting DNA elements in the murine MPO promoter which are functional in 32D cl3 cells, a murine myeloblast cell line which expresses MPO. These DNA elements did not function well in mouse L-cell fibroblasts. Additional mutagenesis of the most active promoter region allowed the delimitation of a functional 20-bp segment. Mutation of the enhancer core motif within this segment was functionally deleterious, and an oligonucleotide containing these base pairs increased the activity of a minimal promoter. This same oligonucleotide, but not a mutant variant, could bind a set of nuclear proteins, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -1 beta), present in 32D cl3 cells but absent from L cells, murine erythroleukemia cells, and SP2 lymphoid cells.

Full text

PDF
2145

Images in this article

2142Image
on p.2142
2148Image
on p.2148
2149Image
on p.2149

Selected References

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

  1. Alessandrini A., Desiderio S. V. Coordination of immunoglobulin DJH transcription and D-to-JH rearrangement by promoter-enhancer approximation. Mol Cell Biol. 1991 Apr;11(4):2096–2107. doi: 10.1128/mcb.11.4.2096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antoniou M., deBoer E., Habets G., Grosveld F. The human beta-globin gene contains multiple regulatory regions: identification of one promoter and two downstream enhancers. EMBO J. 1988 Feb;7(2):377–384. doi: 10.1002/j.1460-2075.1988.tb02824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  4. Carthew R. W., Chodosh L. A., Sharp P. A. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985 Dec;43(2 Pt 1):439–448. doi: 10.1016/0092-8674(85)90174-6. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Evans T., Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989 Sep 8;58(5):877–885. doi: 10.1016/0092-8674(89)90940-9. [DOI] [PubMed] [Google Scholar]
  10. Friedman A. D., Krieder B. L., Venturelli D., Rovera G. Transcriptional regulation of two myeloid-specific genes, myeloperoxidase and lactoferrin, during differentiation of the murine cell line 32D C13. Blood. 1991 Nov 1;78(9):2426–2432. [PubMed] [Google Scholar]
  11. Friedman A. D., Landschulz W. H., McKnight S. L. CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. Genes Dev. 1989 Sep;3(9):1314–1322. doi: 10.1101/gad.3.9.1314. [DOI] [PubMed] [Google Scholar]
  12. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldhamer D. J., Faerman A., Shani M., Emerson C. P., Jr Regulatory elements that control the lineage-specific expression of myoD. Science. 1992 Apr 24;256(5056):538–542. doi: 10.1126/science.1315077. [DOI] [PubMed] [Google Scholar]
  14. Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [PubMed] [Google Scholar]
  15. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  16. Hagman J., Travis A., Grosschedl R. A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. EMBO J. 1991 Nov;10(11):3409–3417. doi: 10.1002/j.1460-2075.1991.tb04905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hickstein D. D., Baker D. M., Gollahon K. A., Back A. L. Identification of the promoter of the myelomonocytic leukocyte integrin CD11b. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2105–2109. doi: 10.1073/pnas.89.6.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Higgs D. R., Wood W. G., Jarman A. P., Sharpe J., Lida J., Pretorius I. M., Ayyub H. A major positive regulatory region located far upstream of the human alpha-globin gene locus. Genes Dev. 1990 Sep;4(9):1588–1601. doi: 10.1101/gad.4.9.1588. [DOI] [PubMed] [Google Scholar]
  19. Hromas R., Collins S. J., Hickstein D., Raskind W., Deaven L. L., O'Hara P., Hagen F. S., Kaushansky K. A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. J Biol Chem. 1991 Aug 5;266(22):14183–14187. [PubMed] [Google Scholar]
  20. Hromas R., Zon L., Friedman A. D. Hematopoietic transcription regulators and the origins of leukemia. Crit Rev Oncol Hematol. 1992 Mar;12(2):167–190. doi: 10.1016/1040-8428(92)90088-8. [DOI] [PubMed] [Google Scholar]
  21. Johnson K. R., Nauseef W. M., Care A., Wheelock M. J., Shane S., Hudson S., Koeffler H. P., Selsted M., Miller C., Rovera G. Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species. Nucleic Acids Res. 1987 Mar 11;15(5):2013–2028. doi: 10.1093/nar/15.5.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johnson K., Gemperlein I., Hudson S., Shane S., Rovera G. Complete nucleotide sequence of the human myeloperoxidase gene. Nucleic Acids Res. 1989 Oct 11;17(19):7985–7986. doi: 10.1093/nar/17.19.7985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Johnson P. F., Landschulz W. H., Graves B. J., McKnight S. L. Identification of a rat liver nuclear protein that binds to the enhancer core element of three animal viruses. Genes Dev. 1987 Apr;1(2):133–146. doi: 10.1101/gad.1.2.133. [DOI] [PubMed] [Google Scholar]
  24. Jorgenson K. F., Antoun G. R., Zipf T. F. Chromatin structural analysis of the 5' end and contiguous flanking region of the myeloperoxidase gene. Blood. 1991 Jan 1;77(1):159–164. [PubMed] [Google Scholar]
  25. KIT S., DUBBS D. R., PIEKARSKI L. J., HSU T. C. DELETION OF THYMIDINE KINASE ACTIVITY FROM L CELLS RESISTANT TO BROMODEOXYURIDINE. Exp Cell Res. 1963 Aug;31:297–312. doi: 10.1016/0014-4827(63)90007-7. [DOI] [PubMed] [Google Scholar]
  26. Kreider B. L., Benezra R., Rovera G., Kadesch T. Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science. 1992 Mar 27;255(5052):1700–1702. doi: 10.1126/science.1372755. [DOI] [PubMed] [Google Scholar]
  27. Leary A. G., Ogawa M., Strauss L. C., Civin C. I. Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes. J Clin Invest. 1984 Dec;74(6):2193–2197. doi: 10.1172/JCI111645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lee K. A., Bindereif A., Green M. R. A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicing. Gene Anal Tech. 1988 Mar-Apr;5(2):22–31. doi: 10.1016/0735-0651(88)90023-4. [DOI] [PubMed] [Google Scholar]
  29. Lübbert M., Miller C. W., Koeffler H. P. Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation. Blood. 1991 Jul 15;78(2):345–356. [PubMed] [Google Scholar]
  30. Matthews W., Jordan C. T., Wiegand G. W., Pardoll D., Lemischka I. R. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 1991 Jun 28;65(7):1143–1152. doi: 10.1016/0092-8674(91)90010-v. [DOI] [PubMed] [Google Scholar]
  31. McKnight S. L., Gavis E. R., Kingsbury R., Axel R. Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. Cell. 1981 Aug;25(2):385–398. doi: 10.1016/0092-8674(81)90057-x. [DOI] [PubMed] [Google Scholar]
  32. Mercurio F., Karin M. Transcription factors AP-3 and AP-2 interact with the SV40 enhancer in a mutually exclusive manner. EMBO J. 1989 May;8(5):1455–1460. doi: 10.1002/j.1460-2075.1989.tb03528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mermelstein F. H., Flores O., Reinberg D. Initiation of transcription by RNA polymerase II. Biochim Biophys Acta. 1989 Sep 21;1009(1):1–10. doi: 10.1016/0167-4781(89)90071-7. [DOI] [PubMed] [Google Scholar]
  34. Morishita K., Tsuchiya M., Asano S., Kaziro Y., Nagata S. Chromosomal gene structure of human myeloperoxidase and regulation of its expression by granulocyte colony-stimulating factor. J Biol Chem. 1987 Nov 5;262(31):15208–15213. [PubMed] [Google Scholar]
  35. Ness S. A., Marknell A., Graf T. The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell. 1989 Dec 22;59(6):1115–1125. doi: 10.1016/0092-8674(89)90767-8. [DOI] [PubMed] [Google Scholar]
  36. Pahl H. L., Rosmarin A. G., Tenen D. G. Characterization of the myeloid-specific CD11b promoter. Blood. 1992 Feb 15;79(4):865–870. [PubMed] [Google Scholar]
  37. Parslow T. G., Granner D. K. Chromatin changes accompany immunoglobulin kappa gene activation: a potential control region within the gene. Nature. 1982 Sep 30;299(5882):449–451. doi: 10.1038/299449a0. [DOI] [PubMed] [Google Scholar]
  38. Parvin J. D., Timmers H. T., Sharp P. A. Promoter specificity of basal transcription factors. Cell. 1992 Mar 20;68(6):1135–1144. doi: 10.1016/0092-8674(92)90084-p. [DOI] [PubMed] [Google Scholar]
  39. Pryzwansky K. B., Martin L. E., Spitznagel J. K. Immunocytochemical localization of myeloperoxidase, lactoferrin, lysozyme and neutral proteases in human monocytes and neutrophilic granulocytes. J Reticuloendothel Soc. 1978 Sep;24(3):295–310. [PubMed] [Google Scholar]
  40. Quintrell N., Lebo R., Varmus H., Bishop J. M., Pettenati M. J., Le Beau M. M., Diaz M. O., Rowley J. D. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells. Mol Cell Biol. 1987 Jun;7(6):2267–2275. doi: 10.1128/mcb.7.6.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosmarin A. G., Levy R., Tenen D. G. Cloning and analysis of the CD18 promoter. Blood. 1992 May 15;79(10):2598–2604. [PubMed] [Google Scholar]
  42. Sagoh T., Yamada M. Transcriptional regulation of myeloperoxidase gene expression in myeloid leukemia HL-60 cells during differentiation into granulocytes and macrophages. Arch Biochem Biophys. 1988 May 1;262(2):599–604. doi: 10.1016/0003-9861(88)90411-0. [DOI] [PubMed] [Google Scholar]
  43. Scheidereit C., Cromlish J. A., Gerster T., Kawakami K., Balmaceda C. G., Currie R. A., Roeder R. G. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature. 1988 Dec 8;336(6199):551–557. doi: 10.1038/336551a0. [DOI] [PubMed] [Google Scholar]
  44. Scott L. M., Civin C. I., Rorth P., Friedman A. D. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 1992 Oct 1;80(7):1725–1735. [PubMed] [Google Scholar]
  45. Seed B., Sheen J. Y. A simple phase-extraction assay for chloramphenicol acyltransferase activity. Gene. 1988 Jul 30;67(2):271–277. doi: 10.1016/0378-1119(88)90403-9. [DOI] [PubMed] [Google Scholar]
  46. Sharp P. A. TATA-binding protein is a classless factor. Cell. 1992 Mar 6;68(5):819–821. doi: 10.1016/0092-8674(92)90023-6. [DOI] [PubMed] [Google Scholar]
  47. Shelley C. S., Arnaout M. A. The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10525–10529. doi: 10.1073/pnas.88.23.10525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. Singh H., LeBowitz J. H., Baldwin A. S., Jr, Sharp P. A. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA. Cell. 1988 Feb 12;52(3):415–423. doi: 10.1016/s0092-8674(88)80034-5. [DOI] [PubMed] [Google Scholar]
  50. Skalnik D. G., Strauss E. C., Orkin S. H. CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91-phox gene promoter. J Biol Chem. 1991 Sep 5;266(25):16736–16744. [PubMed] [Google Scholar]
  51. Smith M. In vitro mutagenesis. Annu Rev Genet. 1985;19:423–462. doi: 10.1146/annurev.ge.19.120185.002231. [DOI] [PubMed] [Google Scholar]
  52. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  53. Straus D. B., Weiss A. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell. 1992 Aug 21;70(4):585–593. doi: 10.1016/0092-8674(92)90428-f. [DOI] [PubMed] [Google Scholar]
  54. Talbot D., Philipsen S., Fraser P., Grosveld F. Detailed analysis of the site 3 region of the human beta-globin dominant control region. EMBO J. 1990 Jul;9(7):2169–2177. doi: 10.1002/j.1460-2075.1990.tb07386.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Tobler A., Miller C. W., Johnson K. R., Selsted M. E., Rovera G., Koeffler H. P. Regulation of gene expression of myeloperoxidase during myeloid differentiation. J Cell Physiol. 1988 Aug;136(2):215–225. doi: 10.1002/jcp.1041360203. [DOI] [PubMed] [Google Scholar]
  56. Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
  57. Valtieri M., Tweardy D. J., Caracciolo D., Johnson K., Mavilio F., Altmann S., Santoli D., Rovera G. Cytokine-dependent granulocytic differentiation. Regulation of proliferative and differentiative responses in a murine progenitor cell line. J Immunol. 1987 Jun 1;138(11):3829–3835. [PubMed] [Google Scholar]
  58. Venturelli D., Bittenbender S., Rovera G. Sequence of the murine myeloperoxidase (MPO) gene. Nucleic Acids Res. 1989 Oct 11;17(19):7987–7988. doi: 10.1093/nar/17.19.7987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Voz M. L., Peers B., Wiedig M. J., Jacquemin P., Belayew A., Martial J. A. Transcriptional regulation by triiodothyronine requires synergistic action of the thyroid receptor with another trans-acting factor. Mol Cell Biol. 1992 Sep;12(9):3991–3997. doi: 10.1128/mcb.12.9.3991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wall L., deBoer E., Grosveld F. The human beta-globin gene 3' enhancer contains multiple binding sites for an erythroid-specific protein. Genes Dev. 1988 Sep;2(9):1089–1100. doi: 10.1101/gad.2.9.1089. [DOI] [PubMed] [Google Scholar]
  61. Warner N. L., Moore M. A., Metcalf D. A transplantable myelomonocytic leukemia in BALB-c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969 Oct;43(4):963–982. [PubMed] [Google Scholar]
  62. Waterman M. L., Fischer W. H., Jones K. A. A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. Genes Dev. 1991 Apr;5(4):656–669. doi: 10.1101/gad.5.4.656. [DOI] [PubMed] [Google Scholar]
  63. Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]
  64. Zsebo K. M., Wypych J., McNiece I. K., Lu H. S., Smith K. A., Karkare S. B., Sachdev R. K., Yuschenkoff V. N., Birkett N. C., Williams L. R. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. Cell. 1990 Oct 5;63(1):195–201. doi: 10.1016/0092-8674(90)90300-4. [DOI] [PubMed] [Google Scholar]
  65. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. van Zonneveld A. J., Curriden S. A., Loskutoff D. J. Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5525–5529. doi: 10.1073/pnas.85.15.5525. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES