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. 1994 Jan;14(1):373–381. doi: 10.1128/mcb.14.1.373

The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor.

D E Zhang 1, C J Hetherington 1, H M Chen 1, D G Tenen 1
PMCID: PMC358386  PMID: 8264604

Abstract

The macrophage colony-stimulating factor (M-CSF) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta. In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage, we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process. Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion. Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor, we investigated whether PU.1 binds and activates the M-CSF receptor promoter. Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site. Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only. Furthermore, PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells. These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor.

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Selected References

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

  1. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  2. Chen C. A., Okayama H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques. 1988 Jul-Aug;6(7):632–638. [PubMed] [Google Scholar]
  3. Chen H. M., Pahl H. L., Scheibe R. J., Zhang D. E., Tenen D. G. The Sp1 transcription factor binds the CD11b promoter specifically in myeloid cells in vivo and is essential for myeloid-specific promoter activity. J Biol Chem. 1993 Apr 15;268(11):8230–8239. [PubMed] [Google Scholar]
  4. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  5. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  6. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  7. Ford A. M., Healy L. E., Bennett C. A., Navarro E., Spooncer E., Greaves M. F. Multilineage phenotypes of interleukin-3-dependent progenitor cells. Blood. 1992 Apr 15;79(8):1962–1971. [PubMed] [Google Scholar]
  8. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galson D. L., Hensold J. O., Bishop T. R., Schalling M., D'Andrea A. D., Jones C., Auron P. E., Housman D. E. Mouse beta-globin DNA-binding protein B1 is identical to a proto-oncogene, the transcription factor Spi-1/PU.1, and is restricted in expression to hematopoietic cells and the testis. Mol Cell Biol. 1993 May;13(5):2929–2941. doi: 10.1128/mcb.13.5.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gisselbrecht S., Fichelson S., Sola B., Bordereaux D., Hampe A., André C., Galibert F., Tambourin P. Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias. Nature. 1987 Sep 17;329(6136):259–261. doi: 10.1038/329259a0. [DOI] [PubMed] [Google Scholar]
  11. Gliniak B. C., Rohrschneider L. R. Expression of the M-CSF receptor is controlled posttranscriptionally by the dominant actions of GM-CSF or multi-CSF. Cell. 1990 Nov 30;63(5):1073–1083. doi: 10.1016/0092-8674(90)90510-l. [DOI] [PubMed] [Google Scholar]
  12. Hagemeier C., Bannister A. J., Cook A., Kouzarides T. The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1580–1584. doi: 10.1073/pnas.90.4.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hipskind R. A., Rao V. N., Mueller C. G., Reddy E. S., Nordheim A. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature. 1991 Dec 19;354(6354):531–534. doi: 10.1038/354531a0. [DOI] [PubMed] [Google Scholar]
  14. Hsu H. C., Yang K., Kharbanda S., Clinton S., Datta R., Stone R. M. All-trans retinoic acid induces monocyte growth factor receptor (c-fms) gene expression in HL-60 leukemia cells. Leukemia. 1993 Mar;7(3):458–462. [PubMed] [Google Scholar]
  15. Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. doi: 10.1016/0092-8674(90)90219-5. [DOI] [PubMed] [Google Scholar]
  16. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  17. Moreau-Gachelin F., Ray D., Mattei M. G., Tambourin P., Tavitian A. The putative oncogene Spi-1: murine chromosomal localization and transcriptional activation in murine acute erythroleukemias. Oncogene. 1989 Dec;4(12):1449–1456. [PubMed] [Google Scholar]
  18. Nienhuis A. W., Bunn H. F., Turner P. H., Gopal T. V., Nash W. G., O'Brien S. J., Sherr C. J. Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome. Cell. 1985 Sep;42(2):421–428. doi: 10.1016/0092-8674(85)90099-6. [DOI] [PubMed] [Google Scholar]
  19. Nordeen S. K. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988 May;6(5):454–458. [PubMed] [Google Scholar]
  20. Pahl H. L., Burn T. C., Tenen D. G. Optimization of transient transfection into human myeloid cell lines using a luciferase reporter gene. Exp Hematol. 1991 Nov;19(10):1038–1041. [PubMed] [Google Scholar]
  21. 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]
  22. Pahl H. L., Scheibe R. J., Zhang D. E., Chen H. M., Galson D. L., Maki R. A., Tenen D. G. The proto-oncogene PU.1 regulates expression of the myeloid-specific CD11b promoter. J Biol Chem. 1993 Mar 5;268(7):5014–5020. [PubMed] [Google Scholar]
  23. Petterson M., Schaffner W. A purine-rich DNA sequence motif present in SV40 and lymphotropic papovavirus binds a lymphoid-specific factor and contributes to enhancer activity in lymphoid cells. Genes Dev. 1987 Nov;1(9):962–972. doi: 10.1101/gad.1.9.962. [DOI] [PubMed] [Google Scholar]
  24. Pongubala J. M., Nagulapalli S., Klemsz M. J., McKercher S. R., Maki R. A., Atchison M. L. PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity. Mol Cell Biol. 1992 Jan;12(1):368–378. doi: 10.1128/mcb.12.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pongubala J. M., Van Beveren C., Nagulapalli S., Klemsz M. J., McKercher S. R., Maki R. A., Atchison M. L. Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science. 1993 Mar 12;259(5101):1622–1625. doi: 10.1126/science.8456286. [DOI] [PubMed] [Google Scholar]
  26. Ray D., Bosselut R., Ghysdael J., Mattei M. G., Tavitian A., Moreau-Gachelin F. Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1. Mol Cell Biol. 1992 Oct;12(10):4297–4304. doi: 10.1128/mcb.12.10.4297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ridge S. A., Worwood M., Oscier D., Jacobs A., Padua R. A. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1377–1380. doi: 10.1073/pnas.87.4.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roberts W. M., Look A. T., Roussel M. F., Sherr C. J. Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes. Cell. 1988 Nov 18;55(4):655–661. doi: 10.1016/0092-8674(88)90224-3. [DOI] [PubMed] [Google Scholar]
  29. Roberts W. M., Shapiro L. H., Ashmun R. A., Look A. T. Transcription of the human colony-stimulating factor-1 receptor gene is regulated by separate tissue-specific promoters. Blood. 1992 Feb 1;79(3):586–593. [PubMed] [Google Scholar]
  30. Roussel M. F., Downing J. R., Rettenmier C. W., Sherr C. J. A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential. Cell. 1988 Dec 23;55(6):979–988. doi: 10.1016/0092-8674(88)90243-7. [DOI] [PubMed] [Google Scholar]
  31. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sariban E., Imamura K., Sherman M., Rothwell V., Pantazis P., Kufe D. Downregulation of c-fms gene expression in human monocytes treated with phorbol esters and colony-stimulating factor 1. Blood. 1989 Jul;74(1):123–129. [PubMed] [Google Scholar]
  33. Satterthwaite A. B., Borson R., Tenen D. G. Regulation of the gene for CD34, a human hematopoietic stem cell antigen, in KG-1 cells. Blood. 1990 Jun 15;75(12):2299–2304. [PubMed] [Google Scholar]
  34. Schuetze S., Paul R., Gliniak B. C., Kabat D. Role of the PU.1 transcription factor in controlling differentiation of Friend erythroleukemia cells. Mol Cell Biol. 1992 Jul;12(7):2967–2975. doi: 10.1128/mcb.12.7.2967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sherr C. J. Colony-stimulating factor-1 receptor. Blood. 1990 Jan 1;75(1):1–12. [PubMed] [Google Scholar]
  36. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  37. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  38. Thompson C. C., Brown T. A., McKnight S. L. Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex. Science. 1991 Aug 16;253(5021):762–768. doi: 10.1126/science.1876833. [DOI] [PubMed] [Google Scholar]
  39. Tobal K., Pagliuca A., Bhatt B., Bailey N., Layton D. M., Mufti G. J. Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia. 1990 Jul;4(7):486–489. [PubMed] [Google Scholar]
  40. Visvader J., Verma I. M. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes. Mol Cell Biol. 1989 Mar;9(3):1336–1341. doi: 10.1128/mcb.9.3.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weber B., Horiguchi J., Luebbers R., Sherman M., Kufe D. Posttranscriptional stabilization of c-fms mRNA by a labile protein during human monocytic differentiation. Mol Cell Biol. 1989 Feb;9(2):769–775. doi: 10.1128/mcb.9.2.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Woolford J., McAuliffe A., Rohrschneider L. R. Activation of the feline c-fms proto-oncogene: multiple alterations are required to generate a fully transformed phenotype. Cell. 1988 Dec 23;55(6):965–977. doi: 10.1016/0092-8674(88)90242-5. [DOI] [PubMed] [Google Scholar]
  43. Zaret K. S., Liu J. K., DiPersio C. M. Site-directed mutagenesis reveals a liver transcription factor essential for the albumin transcriptional enhancer. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5469–5473. doi: 10.1073/pnas.87.14.5469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zhang D. E., Hoyt P. R., Papaconstantinou J. Localization of DNA protein-binding sites in the proximal and distal promoter regions of the mouse alpha-fetoprotein gene. J Biol Chem. 1990 Feb 25;265(6):3382–3391. [PubMed] [Google Scholar]
  45. Ziegler-Heitbrock H. W., Thiel E., Fütterer A., Herzog V., Wirtz A., Riethmüller G. Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes. Int J Cancer. 1988 Mar 15;41(3):456–461. doi: 10.1002/ijc.2910410324. [DOI] [PubMed] [Google Scholar]

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