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. 1993 Jul 15;90(14):6454–6458. doi: 10.1073/pnas.90.14.6454

Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene.

B L Kreider 1, S H Orkin 1, J N Ihle 1
PMCID: PMC46950  PMID: 8341654

Abstract

Inappropriate expression of the Evi-1 zinc-finger gene in hematopoietic cells has been associated with acute myelogenous leukemia and myelodysplastic syndromes in murine models and in humans. Consistent with this, previous studies have shown that aberrant expression of the Evi-1 gene in a myeloid progenitor cell line blocks granulocytic differentiation. Here we demonstrate that the aberrant expression of the Evi-1 gene impairs the normal response of erythroid cells or bone-marrow progenitors to erythropoietin. Erythroid differentiation has been shown to require the GATA-1 transcription factor that binds to a sequence contained within the consensus binding sequence identified for Evi-1. In the studies presented here we also show that Evi-1 can repress GATA-1-dependent transactivation in transient chloramphenicol acetyltransferase assays. Together the data support the hypothesis that inappropriate expression of the Evi-1 gene blocks erythropoiesis by repressing the transcription of a subset of GATA-1 target genes.

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Selected References

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

  1. Bartholomew C., Ihle J. N. Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter. Mol Cell Biol. 1991 Apr;11(4):1820–1828. doi: 10.1128/mcb.11.4.1820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartholomew C., Morishita K., Askew D., Buchberg A., Jenkins N. A., Copeland N. G., Ihle J. N. Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene. Oncogene. 1989 May;4(5):529–534. [PubMed] [Google Scholar]
  3. Chiba T., Ikawa Y., Todokoro K. GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression. Nucleic Acids Res. 1991 Jul 25;19(14):3843–3848. doi: 10.1093/nar/19.14.3843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crotta S., Nicolis S., Ronchi A., Ottolenghi S., Ruzzi L., Shimada Y., Migliaccio A. R., Migliaccio G. Progressive inactivation of the expression of an erythroid transcriptional factor in GM- and G-CSF-dependent myeloid cell lines. Nucleic Acids Res. 1990 Dec 11;18(23):6863–6869. doi: 10.1093/nar/18.23.6863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Andrea A. D., Lodish H. F., Wong G. G. Expression cloning of the murine erythropoietin receptor. Cell. 1989 Apr 21;57(2):277–285. doi: 10.1016/0092-8674(89)90965-3. [DOI] [PubMed] [Google Scholar]
  6. Evans T., Reitman M., Felsenfeld G. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976–5980. doi: 10.1073/pnas.85.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fichelson S., Dreyfus F., Berger R., Melle J., Bastard C., Miclea J. M., Gisselbrecht S. Evi-1 expression in leukemic patients with rearrangements of the 3q25-q28 chromosomal region. Leukemia. 1992 Feb;6(2):93–99. [PubMed] [Google Scholar]
  8. Jotterand Bellomo M., Parlier V., Mühlematter D., Grob J. P., Beris P. Three new cases of chromosome 3 rearrangement in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. Cancer Genet Cytogenet. 1992 Apr;59(2):138–160. doi: 10.1016/0165-4608(92)90208-p. [DOI] [PubMed] [Google Scholar]
  9. Khalili K., Weinmann R. Actin mRNAs in HeLa cells. Stabilization after adenovirus infection. J Mol Biol. 1984 Dec 25;180(4):1007–1021. doi: 10.1016/0022-2836(84)90268-7. [DOI] [PubMed] [Google Scholar]
  10. Kreider B. L., Phillips P. D., Prystowsky M. B., Shirsat N., Pierce J. H., Tushinski R., Rovera G. Induction of the granulocyte-macrophage colony-stimulating factor (CSF) receptor by granulocyte CSF increases the differentiative options of a murine hematopoietic progenitor cell. Mol Cell Biol. 1990 Sep;10(9):4846–4853. doi: 10.1128/mcb.10.9.4846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Martin D. I., Orkin S. H. Transcriptional activation and DNA binding by the erythroid factor GF-1/NF-E1/Eryf 1. Genes Dev. 1990 Nov;4(11):1886–1898. doi: 10.1101/gad.4.11.1886. [DOI] [PubMed] [Google Scholar]
  13. Martin D. I., Tsai S. F., Orkin S. H. Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor. Nature. 1989 Mar 30;338(6214):435–438. doi: 10.1038/338435a0. [DOI] [PubMed] [Google Scholar]
  14. Migliaccio G., Migliaccio A. R., Kreider B. L., Rovera G., Adamson J. W. Selection of lineage-restricted cell lines immortalized at different stages of hematopoietic differentiation from the murine cell line 32D. J Cell Biol. 1989 Aug;109(2):833–841. doi: 10.1083/jcb.109.2.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morishita K., Parganas E., Matsugi T., Ihle J. N. Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor. Mol Cell Biol. 1992 Jan;12(1):183–189. doi: 10.1128/mcb.12.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morishita K., Parganas E., William C. L., Whittaker M. H., Drabkin H., Oval J., Taetle R., Valentine M. B., Ihle J. N. Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300-400 kilobases on chromosome band 3q26. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3937–3941. doi: 10.1073/pnas.89.9.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morishita K., Parker D. S., Mucenski M. L., Jenkins N. A., Copeland N. G., Ihle J. N. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Cell. 1988 Sep 9;54(6):831–840. doi: 10.1016/s0092-8674(88)91175-0. [DOI] [PubMed] [Google Scholar]
  18. Mucenski M. L., Taylor B. A., Ihle J. N., Hartley J. W., Morse H. C., 3rd, Jenkins N. A., Copeland N. G. Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors. Mol Cell Biol. 1988 Jan;8(1):301–308. doi: 10.1128/mcb.8.1.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Orkin S. H. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
  20. Perkins A. S., Fishel R., Jenkins N. A., Copeland N. G. Evi-1, a murine zinc finger proto-oncogene, encodes a sequence-specific DNA-binding protein. Mol Cell Biol. 1991 May;11(5):2665–2674. doi: 10.1128/mcb.11.5.2665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pevny L., Simon M. C., Robertson E., Klein W. H., Tsai S. F., D'Agati V., Orkin S. H., Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. doi: 10.1038/349257a0. [DOI] [PubMed] [Google Scholar]
  22. Rahuel C., Vinit M. A., Lemarchandel V., Cartron J. P., Roméo P. H. Erythroid-specific activity of the glycophorin B promoter requires GATA-1 mediated displacement of a repressor. EMBO J. 1992 Nov;11(11):4095–4102. doi: 10.1002/j.1460-2075.1992.tb05502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsai S. F., Strauss E., Orkin S. H. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev. 1991 Jun;5(6):919–931. doi: 10.1101/gad.5.6.919. [DOI] [PubMed] [Google Scholar]
  24. Visvader J. E., Elefanty A. G., Strasser A., Adams J. M. GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. EMBO J. 1992 Dec;11(12):4557–4564. doi: 10.1002/j.1460-2075.1992.tb05557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Weintraub H., Tapscott S. J., Davis R. L., Thayer M. J., Adam M. A., Lassar A. B., Miller A. D. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434–5438. doi: 10.1073/pnas.86.14.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zon L. I., Youssoufian H., Mather C., Lodish H. F., Orkin S. H. Activation of the erythropoietin receptor promoter by transcription factor GATA-1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10638–10641. doi: 10.1073/pnas.88.23.10638. [DOI] [PMC free article] [PubMed] [Google Scholar]

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