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. 1993 Apr;13(4):2235–2246. doi: 10.1128/mcb.13.4.2235

Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart.

R J Arceci 1, A A King 1, M C Simon 1, S H Orkin 1, D B Wilson 1
PMCID: PMC359544  PMID: 8455608

Abstract

We report the cDNA cloning and characterization of mouse GATA-4, a new member of the family of zinc finger transcription factors that bind a core GATA motif. GATA-4 cDNA was identified by screening a 6.5-day mouse embryo library with oligonucleotide probes corresponding to a highly conserved region of the finger domains. Like other proteins of the family, GATA-4 is approximately 50 kDa in size and contains two zinc finger domains of the form C-X-N-C-(X17)-C-N-X-C. Cotransfection assays in heterologous cells demonstrate that GATA-4 trans activates reporter constructs containing GATA promoter elements. Northern (RNA) analysis and in situ hybridization show that GATA-4 mRNA is expressed in the heart, intestinal epithelium, primitive endoderm, and gonads. Retinoic acid-induced differentiation of mouse F9 cells into visceral or parietal endoderm is accompanied by increased expression of GATA-4 mRNA and protein. In vitro differentiation of embryonic stem cells into embryoid bodies is also associated with increased GATA-4 expression. We conclude that GATA-4 is a tissue-specific, retinoic acid-inducible, and developmentally regulated transcription factor. On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads.

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Selected References

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

  1. Arceci R. J., Shanahan F., Stanley E. R., Pollard J. W. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8818–8822. doi: 10.1073/pnas.86.22.8818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cavener D. R., Ray S. C. Eukaryotic start and stop translation sites. Nucleic Acids Res. 1991 Jun 25;19(12):3185–3192. doi: 10.1093/nar/19.12.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  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. Darrow A. L., Rickles R. J., Strickland S. Maintenance and use of F9 teratocarcinoma cells. Methods Enzymol. 1990;190:110–117. doi: 10.1016/0076-6879(90)90015-s. [DOI] [PubMed] [Google Scholar]
  7. Davis M. A., Hynes M. J. Complementation of areA- regulatory gene mutations of Aspergillus nidulans by the heterologous regulatory gene nit-2 of Neurospora crassa. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3753–3757. doi: 10.1073/pnas.84.11.3753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doetschman T. C., Eistetter H., Katz M., Schmidt W., Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed] [Google Scholar]
  9. Dorfman D. M., Wilson D. B., Bruns G. A., Orkin S. H. Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells. J Biol Chem. 1992 Jan 15;267(2):1279–1285. [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. Fu Y. H., Marzluf G. A. nit-2, the major nitrogen regulatory gene of Neurospora crassa, encodes a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1990 Mar;10(3):1056–1065. doi: 10.1128/mcb.10.3.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gudas L. J. Assays for expression of genes regulated by retinoic acid in murine teratocarcinoma cell lines. Methods Enzymol. 1990;190:131–140. doi: 10.1016/0076-6879(90)90017-u. [DOI] [PubMed] [Google Scholar]
  16. Ho I. C., Vorhees P., Marin N., Oakley B. K., Tsai S. F., Orkin S. H., Leiden J. M. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. EMBO J. 1991 May;10(5):1187–1192. doi: 10.1002/j.1460-2075.1991.tb08059.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hogan B. L., Taylor A., Adamson E. Cell interactions modulate embryonal carcinoma cell differentiation into parietal or visceral endoderm. Nature. 1981 May 21;291(5812):235–237. doi: 10.1038/291235a0. [DOI] [PubMed] [Google Scholar]
  18. Joulin V., Bories D., Eléouet J. F., Labastie M. C., Chrétien S., Mattéi M. G., Roméo P. H. A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J. 1991 Jul;10(7):1809–1816. doi: 10.1002/j.1460-2075.1991.tb07706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ko L. J., Yamamoto M., Leonard M. W., George K. M., Ting P., Engel J. D. Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. Mol Cell Biol. 1991 May;11(5):2778–2784. doi: 10.1128/mcb.11.5.2778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kudla B., Caddick M. X., Langdon T., Martinez-Rossi N. M., Bennett C. F., Sibley S., Davies R. W., Arst H. N., Jr The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 1990 May;9(5):1355–1364. doi: 10.1002/j.1460-2075.1990.tb08250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Lee M. E., Bloch K. D., Clifford J. A., Quertermous T. Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence. J Biol Chem. 1990 Jun 25;265(18):10446–10450. [PubMed] [Google Scholar]
  23. Lee M. E., Temizer D. H., Clifford J. A., Quertermous T. Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem. 1991 Aug 25;266(24):16188–16192. [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. 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]
  27. Minehart P. L., Magasanik B. Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1991 Dec;11(12):6216–6228. doi: 10.1128/mcb.11.12.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Orkin S. H. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
  29. Orkin S. H. Globin gene regulation and switching: circa 1990. Cell. 1990 Nov 16;63(4):665–672. doi: 10.1016/0092-8674(90)90133-y. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Plumb M., Frampton J., Wainwright H., Walker M., Macleod K., Goodwin G., Harrison P. GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression. Nucleic Acids Res. 1989 Jan 11;17(1):73–92. doi: 10.1093/nar/17.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Spieth J., Shim Y. H., Lea K., Conrad R., Blumenthal T. elt-1, an embryonically expressed Caenorhabditis elegans gene homologous to the GATA transcription factor family. Mol Cell Biol. 1991 Sep;11(9):4651–4659. doi: 10.1128/mcb.11.9.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Strauss E. C., Andrews N. C., Higgs D. R., Orkin S. H. In vivo footprinting of the human alpha-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction. Mol Cell Biol. 1992 May;12(5):2135–2142. doi: 10.1128/mcb.12.5.2135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sweetser D. A., Hauft S. M., Hoppe P. C., Birkenmeier E. H., Gordon J. I. Transgenic mice containing intestinal fatty acid-binding protein-human growth hormone fusion genes exhibit correct regional and cell-specific expression of the reporter gene in their small intestine. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9611–9615. doi: 10.1073/pnas.85.24.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Traber P. G., Wu G. D., Wang W. Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene. Mol Cell Biol. 1992 Aug;12(8):3614–3627. doi: 10.1128/mcb.12.8.3614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Trainor C. D., Evans T., Felsenfeld G., Boguski M. S. Structure and evolution of a human erythroid transcription factor. Nature. 1990 Jan 4;343(6253):92–96. doi: 10.1038/343092a0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Weng D. E., Morgan R. A., Gearhart J. D. Estimates of mRNA abundance in the mouse blastocyst based on cDNA library analysis. Mol Reprod Dev. 1989;1(4):233–241. doi: 10.1002/mrd.1080010403. [DOI] [PubMed] [Google Scholar]
  42. Wilson D. B., Dorfman D. M., Orkin S. H. A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol. 1990 Sep;10(9):4854–4862. doi: 10.1128/mcb.10.9.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Witte O. N. Steel locus defines new multipotent growth factor. Cell. 1990 Oct 5;63(1):5–6. doi: 10.1016/0092-8674(90)90280-r. [DOI] [PubMed] [Google Scholar]
  44. Wu G. D., Wang W., Traber P. G. Isolation and characterization of the human sucrase-isomaltase gene and demonstration of intestine-specific transcriptional elements. J Biol Chem. 1992 Apr 15;267(11):7863–7870. [PubMed] [Google Scholar]
  45. 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]
  46. Zon L. I., Gurish M. F., Stevens R. L., Mather C., Reynolds D. S., Austen K. F., Orkin S. H. GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. J Biol Chem. 1991 Dec 5;266(34):22948–22953. [PubMed] [Google Scholar]
  47. 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]
  48. Zon L. I., Tsai S. F., Burgess S., Matsudaira P., Bruns G. A., Orkin S. H. The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome. Proc Natl Acad Sci U S A. 1990 Jan;87(2):668–672. doi: 10.1073/pnas.87.2.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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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