Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 May;14(5):3108–3114. doi: 10.1128/mcb.14.5.3108

Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells.

M H Baron 1, S M Farrington 1
PMCID: PMC358678  PMID: 8164666

Abstract

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.

Full text

PDF
3108

Images in this article

3110Image
on p.3110
3110Image
on p.3110
3111Image
on p.3111
3112Image
on p.3112

Selected References

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

  1. Andrews N. C., Erdjument-Bromage H., Davidson M. B., Tempst P., Orkin S. H. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Nature. 1993 Apr 22;362(6422):722–728. doi: 10.1038/362722a0. [DOI] [PubMed] [Google Scholar]
  2. Baron M. H., Maniatis T. Rapid reprogramming of globin gene expression in transient heterokaryons. Cell. 1986 Aug 15;46(4):591–602. doi: 10.1016/0092-8674(86)90885-8. [DOI] [PubMed] [Google Scholar]
  3. Baron M. H., Maniatis T. Regulated expression of human alpha- and beta-globin genes in transient heterokaryons. Mol Cell Biol. 1991 Mar;11(3):1239–1247. doi: 10.1128/mcb.11.3.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baron M. H. Reversibility of the differentiated state in somatic cells. Curr Opin Cell Biol. 1993 Dec;5(6):1050–1056. doi: 10.1016/0955-0674(93)90091-4. [DOI] [PubMed] [Google Scholar]
  5. Barton M. C., Madani N., Emerson B. M. The erythroid protein cGATA-1 functions with a stage-specific factor to activate transcription of chromatin-assembled beta-globin genes. Genes Dev. 1993 Sep;7(9):1796–1809. doi: 10.1101/gad.7.9.1796. [DOI] [PubMed] [Google Scholar]
  6. Blau H. M., Chiu C. P., Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983 Apr;32(4):1171–1180. doi: 10.1016/0092-8674(83)90300-8. [DOI] [PubMed] [Google Scholar]
  7. Blau H. M. Differentiation requires continuous active control. Annu Rev Biochem. 1992;61:1213–1230. doi: 10.1146/annurev.bi.61.070192.010025. [DOI] [PubMed] [Google Scholar]
  8. Braun T., Bober E., Buschhausen-Denker G., Kohtz S., Grzeschik K. H., Arnold H. H., Kotz S. Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. EMBO J. 1989 Dec 1;8(12):3617–3625. doi: 10.1002/j.1460-2075.1989.tb08535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Briegel K., Lim K. C., Plank C., Beug H., Engel J. D., Zenke M. Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. Genes Dev. 1993 Jun;7(6):1097–1109. doi: 10.1101/gad.7.6.1097. [DOI] [PubMed] [Google Scholar]
  10. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  11. Chiu C. P., Blau H. M. Reprogramming cell differentiation in the absence of DNA synthesis. Cell. 1984 Jul;37(3):879–887. doi: 10.1016/0092-8674(84)90423-9. [DOI] [PubMed] [Google Scholar]
  12. Dillon N., Grosveld F. Transcriptional regulation of multigene loci: multilevel control. Trends Genet. 1993 Apr;9(4):134–137. doi: 10.1016/0168-9525(93)90208-y. [DOI] [PubMed] [Google Scholar]
  13. Engel J. D., George K. M., Ko L. J., Kornhauser J. M., Leonard M. W., Ting P., Yamamoto M. Transcription factor regulation of hematopoietic lineage cells. Semin Hematol. 1991 Apr;28(2):158–169. [PubMed] [Google Scholar]
  14. Evans T., Felsenfeld G., Reitman M. Control of globin gene transcription. Annu Rev Cell Biol. 1990;6:95–124. doi: 10.1146/annurev.cb.06.110190.000523. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Evans T., Felsenfeld G. trans-Activation of a globin promoter in nonerythroid cells. Mol Cell Biol. 1991 Feb;11(2):843–853. doi: 10.1128/mcb.11.2.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Fong T. C., Emerson B. M. The erythroid-specific protein cGATA-1 mediates distal enhancer activity through a specialized beta-globin TATA box. Genes Dev. 1992 Apr;6(4):521–532. doi: 10.1101/gad.6.4.521. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Gong Q., Dean A. Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2. Mol Cell Biol. 1993 Feb;13(2):911–917. doi: 10.1128/mcb.13.2.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
  22. Hannon R., Evans T., Felsenfeld G., Gould H. Structure and promoter activity of the gene for the erythroid transcription factor GATA-1. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3004–3008. doi: 10.1073/pnas.88.8.3004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hardeman E. C., Chiu C. P., Minty A., Blau H. M. The pattern of actin expression in human fibroblast x mouse muscle heterokaryons suggests that human muscle regulatory factors are produced. Cell. 1986 Oct 10;47(1):123–130. doi: 10.1016/0092-8674(86)90373-9. [DOI] [PubMed] [Google Scholar]
  24. Hofer E., Hofer-Warbinek R., Darnell J. E., Jr Globin RNA transcription: a possible termination site and demonstration of transcriptional control correlated with altered chromatin structure. Cell. 1982 Jul;29(3):887–893. doi: 10.1016/0092-8674(82)90450-0. [DOI] [PubMed] [Google Scholar]
  25. Leonard M. W., Lim K. C., Engel J. D. Expression of the chicken GATA factor family during early erythroid development and differentiation. Development. 1993 Oct;119(2):519–531. doi: 10.1242/dev.119.2.519. [DOI] [PubMed] [Google Scholar]
  26. Leonard M., Brice M., Engel J. D., Papayannopoulou T. Dynamics of GATA transcription factor expression during erythroid differentiation. Blood. 1993 Aug 15;82(4):1071–1079. [PubMed] [Google Scholar]
  27. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Martin D. I., Zon L. I., Mutter G., Orkin S. H. Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. Nature. 1990 Mar 29;344(6265):444–447. doi: 10.1038/344444a0. [DOI] [PubMed] [Google Scholar]
  31. Mignotte V., Wall L., deBoer E., Grosveld F., Romeo P. H. Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. Nucleic Acids Res. 1989 Jan 11;17(1):37–54. doi: 10.1093/nar/17.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Miller I. J., Bieker J. J. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Mol Cell Biol. 1993 May;13(5):2776–2786. doi: 10.1128/mcb.13.5.2776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mével-Ninio M., Weiss M. C. Immunofluorescence analysis of the time-course of extinction, reexpression, and activation of albumin production in rat hepatoma-mouse fibroblast heterokaryons and hybrids. J Cell Biol. 1981 Aug;90(2):339–350. doi: 10.1083/jcb.90.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Orkin S. H. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
  35. Pavlath G. K., Blau H. M. Expression of muscle genes in heterokaryons depends on gene dosage. J Cell Biol. 1986 Jan;102(1):124–130. doi: 10.1083/jcb.102.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Peterson C. A., Gordon H., Hall Z. W., Paterson B. M., Blau H. M. Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant. Cell. 1990 Aug 10;62(3):493–502. doi: 10.1016/0092-8674(90)90014-6. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Robertson E., Bradley A., Kuehn M., Evans M. Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature. 1986 Oct 2;323(6087):445–448. doi: 10.1038/323445a0. [DOI] [PubMed] [Google Scholar]
  39. Romeo P. H., Prandini M. H., Joulin V., Mignotte V., Prenant M., Vainchenker W., Marguerie G., Uzan G. Megakaryocytic and erythrocytic lineages share specific transcription factors. Nature. 1990 Mar 29;344(6265):447–449. doi: 10.1038/344447a0. [DOI] [PubMed] [Google Scholar]
  40. Simon M. C., Pevny L., Wiles M. V., Keller G., Costantini F., Orkin S. H. Rescue of erythroid development in gene targeted GATA-1- mouse embryonic stem cells. Nat Genet. 1992 May;1(2):92–98. doi: 10.1038/ng0592-92. [DOI] [PubMed] [Google Scholar]
  41. Thayer M. J., Tapscott S. J., Davis R. L., Wright W. E., Lassar A. B., Weintraub H. Positive autoregulation of the myogenic determination gene MyoD1. Cell. 1989 Jul 28;58(2):241–248. doi: 10.1016/0092-8674(89)90838-6. [DOI] [PubMed] [Google Scholar]
  42. Thayer M. J., Weintraub H. Activation and repression of myogenesis in somatic cell hybrids: evidence for trans-negative regulation of MyoD in primary fibroblasts. Cell. 1990 Oct 5;63(1):23–32. doi: 10.1016/0092-8674(90)90285-m. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. 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]
  45. 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]
  46. Walters M., Martin D. I. Functional erythroid promoters created by interaction of the transcription factor GATA-1 with CACCC and AP-1/NFE-2 elements. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10444–10448. doi: 10.1073/pnas.89.21.10444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]
  48. Youssoufian H., Zon L. I., Orkin S. H., D'Andrea A. D., Lodish H. F. Structure and transcription of the mouse erythropoietin receptor gene. Mol Cell Biol. 1990 Jul;10(7):3675–3682. doi: 10.1128/mcb.10.7.3675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
  50. Zon L. I., Mather C., Burgess S., Bolce M. E., Harland R. M., Orkin S. H. Expression of GATA-binding proteins during embryonic development in Xenopus laevis. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10642–10646. doi: 10.1073/pnas.88.23.10642. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES