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. 1993 May;12(5):2027–2038. doi: 10.1002/j.1460-2075.1993.tb05852.x

Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors.

O Burk 1, S Mink 1, M Ringwald 1, K H Klempnauer 1
PMCID: PMC413425  PMID: 8491193

Abstract

The retroviral oncogene v-myb encodes a transcriptional activator which is responsible for the activation of the mim-1 gene in myelomonocytic cells transformed by v-myb. The mim-1 promoter contains several myb consensus binding sites and has previously been shown to be regulated directly by v-myb. Here we report that the mim-1 gene is activated synergistically by v-myb and different C/EBP transcription factors. We have cloned a chicken C/EBP-related gene that is highly expressed in myeloid cells and identified it as the chicken homolog of C/EBP beta. A dominant-negative variant of chicken C/EBP beta interferes with the v-myb induced activation of the mim-1 gene in these cells, suggesting that C/EBP beta or another C/EBP transcription factor is required for the activation of mim-1 by v-myb. We found that C/EBP beta and other C/EBP transcription factors confer to fibroblasts the ability to induce the mim-1 gene in the presence of v-myb. Finally we show that, in contrast to v-myb, c-myb synergizes with C/EBP transcription factors only at low concentrations of c-myb protein. Our results suggest a role for C/EBP beta, and possibly for other C/EBP transcription factors, in v-myb function and in myeloid-specific gene activation.

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  1. Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barberis A., Superti-Furga G., Busslinger M. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell. 1987 Jul 31;50(3):347–359. doi: 10.1016/0092-8674(87)90489-2. [DOI] [PubMed] [Google Scholar]
  3. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  4. Burk O., Klempnauer K. H. Estrogen-dependent alterations in differentiation state of myeloid cells caused by a v-myb/estrogen receptor fusion protein. EMBO J. 1991 Dec;10(12):3713–3719. doi: 10.1002/j.1460-2075.1991.tb04939.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Carey M., Lin Y. S., Green M. R., Ptashne M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature. 1990 May 24;345(6273):361–364. doi: 10.1038/345361a0. [DOI] [PubMed] [Google Scholar]
  7. Clarke M. F., Kukowska-Latallo J. F., Westin E., Smith M., Prochownik E. V. Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. Mol Cell Biol. 1988 Feb;8(2):884–892. doi: 10.1128/mcb.8.2.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Descombes P., Chojkier M., Lichtsteiner S., Falvey E., Schibler U. LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes Dev. 1990 Sep;4(9):1541–1551. doi: 10.1101/gad.4.9.1541. [DOI] [PubMed] [Google Scholar]
  9. Dudek H., Tantravahi R. V., Rao V. N., Reddy E. S., Reddy E. P. Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1291–1295. doi: 10.1073/pnas.89.4.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evan G. I., Lewis G. K., Bishop J. M. Isolation of monoclonal antibodies specific for products of avian oncogene myb. Mol Cell Biol. 1984 Dec;4(12):2843–2850. doi: 10.1128/mcb.4.12.2843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foos G., Grimm S., Klempnauer K. H. Functional antagonism between members of the myb family: B-myb inhibits v-myb-induced gene activation. EMBO J. 1992 Dec;11(12):4619–4629. doi: 10.1002/j.1460-2075.1992.tb05564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Gewirtz A. M., Calabretta B. A c-myb antisense oligodeoxynucleotide inhibits normal human hematopoiesis in vitro. Science. 1988 Dec 2;242(4883):1303–1306. doi: 10.1126/science.2461588. [DOI] [PubMed] [Google Scholar]
  14. Goff S. A., Cone K. C., Chandler V. L. Functional analysis of the transcriptional activator encoded by the maize B gene: evidence for a direct functional interaction between two classes of regulatory proteins. Genes Dev. 1992 May;6(5):864–875. doi: 10.1101/gad.6.5.864. [DOI] [PubMed] [Google Scholar]
  15. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  16. Grässer F. A., Graf T., Lipsick J. S. Protein truncation is required for the activation of the c-myb proto-oncogene. Mol Cell Biol. 1991 Aug;11(8):3987–3996. doi: 10.1128/mcb.11.8.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ibanez C. E., Lipsick J. S. trans activation of gene expression by v-myb. Mol Cell Biol. 1990 May;10(5):2285–2293. doi: 10.1128/mcb.10.5.2285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Introna M., Golay J., Frampton J., Nakano T., Ness S. A., Graf T. Mutations in v-myb alter the differentiation of myelomonocytic cells transformed by the oncogene. Cell. 1990 Dec 21;63(6):1289–1297. doi: 10.1016/0092-8674(90)90424-d. [DOI] [PubMed] [Google Scholar]
  19. Jain V. K., Magrath I. T. A chemiluminescent assay for quantitation of beta-galactosidase in the femtogram range: application to quantitation of beta-galactosidase in lacZ-transfected cells. Anal Biochem. 1991 Nov 15;199(1):119–124. doi: 10.1016/0003-2697(91)90278-2. [DOI] [PubMed] [Google Scholar]
  20. Klempnauer K. H., Arnold H., Biedenkapp H. Activation of transcription by v-myb: evidence for two different mechanisms. Genes Dev. 1989 Oct;3(10):1582–1589. doi: 10.1101/gad.3.10.1582. [DOI] [PubMed] [Google Scholar]
  21. Klempnauer K. H., Bishop J. M. Transduction of c-myb into avian myeloblastosis virus: locating points of recombination within the cellular gene. J Virol. 1983 Dec;48(3):565–572. doi: 10.1128/jvi.48.3.565-572.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klempnauer K. H., Bonifer C., Sippel A. E. Identification and characterization of the protein encoded by the human c-myb proto-oncogene. EMBO J. 1986 Aug;5(8):1903–1911. doi: 10.1002/j.1460-2075.1986.tb04443.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klempnauer K. H., Gonda T. J., Bishop J. M. Nucleotide sequence of the retroviral leukemia gene v-myb and its cellular progenitor c-myb: the architecture of a transduced oncogene. Cell. 1982 Dec;31(2 Pt 1):453–463. doi: 10.1016/0092-8674(82)90138-6. [DOI] [PubMed] [Google Scholar]
  24. Klempnauer K. H., Ramsay G., Bishop J. M., Moscovici M. G., Moscovici C., McGrath J. P., Levinson A. D. The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb. Cell. 1983 Jun;33(2):345–355. doi: 10.1016/0092-8674(83)90416-6. [DOI] [PubMed] [Google Scholar]
  25. Klempnauer K. H., Sippel A. E. The highly conserved amino-terminal region of the protein encoded by the v-myb oncogene functions as a DNA-binding domain. EMBO J. 1987 Sep;6(9):2719–2725. doi: 10.1002/j.1460-2075.1987.tb02565.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  27. Lin Y. S., Carey M., Ptashne M., Green M. R. How different eukaryotic transcriptional activators can cooperate promiscuously. Nature. 1990 May 24;345(6273):359–361. doi: 10.1038/345359a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Metz R., Ziff E. cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription. Genes Dev. 1991 Oct;5(10):1754–1766. doi: 10.1101/gad.5.10.1754. [DOI] [PubMed] [Google Scholar]
  30. Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
  31. Mucenski M. L., McLain K., Kier A. B., Swerdlow S. H., Schreiner C. M., Miller T. A., Pietryga D. W., Scott W. J., Jr, Potter S. S. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell. 1991 May 17;65(4):677–689. doi: 10.1016/0092-8674(91)90099-k. [DOI] [PubMed] [Google Scholar]
  32. Natsuka S., Akira S., Nishio Y., Hashimoto S., Sugita T., Isshiki H., Kishimoto T. Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood. 1992 Jan 15;79(2):460–466. [PubMed] [Google Scholar]
  33. 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]
  34. Nishina Y., Nakagoshi H., Imamoto F., Gonda T. J., Ishii S. Trans-activation by the c-myb proto-oncogene. Nucleic Acids Res. 1989 Jan 11;17(1):107–117. doi: 10.1093/nar/17.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nordeen S. K. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988 May;6(5):454–458. [PubMed] [Google Scholar]
  36. Oehler T., Arnold H., Biedenkapp H., Klempnauer K. H. Characterization of the v-myb DNA binding domain. Nucleic Acids Res. 1990 Apr 11;18(7):1703–1710. doi: 10.1093/nar/18.7.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pettersson M., Schaffner W. Synergistic activation of transcription by multiple binding sites for NF-kappa B even in absence of co-operative factor binding to DNA. J Mol Biol. 1990 Jul 20;214(2):373–380. doi: 10.1016/0022-2836(90)90187-q. [DOI] [PubMed] [Google Scholar]
  38. Poli V., Mancini F. P., Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990 Nov 2;63(3):643–653. doi: 10.1016/0092-8674(90)90459-r. [DOI] [PubMed] [Google Scholar]
  39. Quéva C., Ness S. A., Grässer F. A., Graf T., Vandenbunder B., Stéhelin D. Expression patterns of c-myb and of v-myb induced myeloid-1 (mim-1) gene during the development of the chick embryo. Development. 1992 Jan;114(1):125–133. doi: 10.1242/dev.114.1.125. [DOI] [PubMed] [Google Scholar]
  40. Roman C., Platero J. S., Shuman J., Calame K. Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP. Genes Dev. 1990 Aug;4(8):1404–1415. doi: 10.1101/gad.4.8.1404. [DOI] [PubMed] [Google Scholar]
  41. Ron D., Habener J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992 Mar;6(3):439–453. doi: 10.1101/gad.6.3.439. [DOI] [PubMed] [Google Scholar]
  42. Sakura H., Kanei-Ishii C., Nagase T., Nakagoshi H., Gonda T. J., Ishii S. Delineation of three functional domains of the transcriptional activator encoded by the c-myb protooncogene. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5758–5762. doi: 10.1073/pnas.86.15.5758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Selvakumaran M., Liebermann D. A., Hoffman-Liebermann B. Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis. Mol Cell Biol. 1992 Jun;12(6):2493–2500. doi: 10.1128/mcb.12.6.2493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shen-Ong G. L. The myb oncogene. Biochim Biophys Acta. 1990 Jun 1;1032(1):39–52. doi: 10.1016/0304-419x(90)90011-o. [DOI] [PubMed] [Google Scholar]
  46. Sterneck E., Müller C., Katz S., Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992 Jan;11(1):115–126. doi: 10.1002/j.1460-2075.1992.tb05034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tice-Baldwin K., Fink G. R., Arndt K. T. BAS1 has a Myb motif and activates HIS4 transcription only in combination with BAS2. Science. 1989 Nov 17;246(4932):931–935. doi: 10.1126/science.2683089. [DOI] [PubMed] [Google Scholar]
  48. Todokoro K., Watson R. J., Higo H., Amanuma H., Kuramochi S., Yanagisawa H., Ikawa Y. Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8900–8904. doi: 10.1073/pnas.85.23.8900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Umek R. M., Friedman A. D., McKnight S. L. CCAAT-enhancer binding protein: a component of a differentiation switch. Science. 1991 Jan 18;251(4991):288–292. doi: 10.1126/science.1987644. [DOI] [PubMed] [Google Scholar]
  50. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  51. Weston K., Bishop J. M. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell. 1989 Jul 14;58(1):85–93. doi: 10.1016/0092-8674(89)90405-4. [DOI] [PubMed] [Google Scholar]
  52. Williams S. C., Cantwell C. A., Johnson P. F. A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Genes Dev. 1991 Sep;5(9):1553–1567. doi: 10.1101/gad.5.9.1553. [DOI] [PubMed] [Google Scholar]
  53. 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]

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