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. 1997 May 15;16(10):2874–2882. doi: 10.1093/emboj/16.10.2874

The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains.

P V Pedone 1, J G Omichinski 1, P Nony 1, C Trainor 1, A M Gronenborn 1, G M Clore 1, G Felsenfeld 1
PMCID: PMC1169895  PMID: 9184231

Abstract

The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo.

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Selected References

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  1. 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]
  2. 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]
  3. Fu Y. H., Marzluf G. A. nit-2, the major positive-acting nitrogen regulatory gene of Neurospora crassa, encodes a sequence-specific DNA-binding protein. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5331–5335. doi: 10.1073/pnas.87.14.5331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. George K. M., Leonard M. W., Roth M. E., Lieuw K. H., Kioussis D., Grosveld F., Engel J. D. Embryonic expression and cloning of the murine GATA-3 gene. Development. 1994 Sep;120(9):2673–2686. doi: 10.1242/dev.120.9.2673. [DOI] [PubMed] [Google Scholar]
  5. Ito E., Toki T., Ishihara H., Ohtani H., Gu L., Yokoyama M., Engel J. D., Yamamoto M. Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature. 1993 Apr 1;362(6419):466–468. doi: 10.1038/362466a0. [DOI] [PubMed] [Google Scholar]
  6. Kelley C., Blumberg H., Zon L. I., Evans T. GATA-4 is a novel transcription factor expressed in endocardium of the developing heart. Development. 1993 Jul;118(3):817–827. doi: 10.1242/dev.118.3.817. [DOI] [PubMed] [Google Scholar]
  7. Ko L. J., Engel J. D. DNA-binding specificities of the GATA transcription factor family. Mol Cell Biol. 1993 Jul;13(7):4011–4022. doi: 10.1128/mcb.13.7.4011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Laverriere A. C., MacNeill C., Mueller C., Poelmann R. E., Burch J. B., Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994 Sep 16;269(37):23177–23184. [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Merika M., Orkin S. H. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol. 1993 Jul;13(7):3999–4010. doi: 10.1128/mcb.13.7.3999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mouthon M. A., Bernard O., Mitjavila M. T., Romeo P. H., Vainchenker W., Mathieu-Mahul D. Expression of tal-1 and GATA-binding proteins during human hematopoiesis. Blood. 1993 Feb 1;81(3):647–655. [PubMed] [Google Scholar]
  14. Omichinski J. G., Clore G. M., Schaad O., Felsenfeld G., Trainor C., Appella E., Stahl S. J., Gronenborn A. M. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science. 1993 Jul 23;261(5120):438–446. doi: 10.1126/science.8332909. [DOI] [PubMed] [Google Scholar]
  15. Omichinski J. G., Trainor C., Evans T., Gronenborn A. M., Clore G. M., Felsenfeld G. A small single-"finger" peptide from the erythroid transcription factor GATA-1 binds specifically to DNA as a zinc or iron complex. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1676–1680. doi: 10.1073/pnas.90.5.1676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Oosterwegel M., Timmerman J., Leiden J., Clevers H. Expression of GATA-3 during lymphocyte differentiation and mouse embryogenesis. Dev Immunol. 1992;3(1):1–11. doi: 10.1155/1992/27903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Orkin S. H. GATA-binding transcription factors in hematopoietic cells. Blood. 1992 Aug 1;80(3):575–581. [PubMed] [Google Scholar]
  18. Pandolfi P. P., Roth M. E., Karis A., Leonard M. W., Dzierzak E., Grosveld F. G., Engel J. D., Lindenbaum M. H. Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet. 1995 Sep;11(1):40–44. doi: 10.1038/ng0995-40. [DOI] [PubMed] [Google Scholar]
  19. Pedone P. V., Ghirlando R., Clore G. M., Gronenborn A. M., Felsenfeld G., Omichinski J. G. The single Cys2-His2 zinc finger domain of the GAGA protein flanked by basic residues is sufficient for high-affinity specific DNA binding. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2822–2826. doi: 10.1073/pnas.93.7.2822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Shim Y. H., Bonner J. J., Blumenthal T. Activity of a C. elegans GATA transcription factor, ELT-1, expressed in yeast. J Mol Biol. 1995 Nov 10;253(5):665–676. doi: 10.1006/jmbi.1995.0581. [DOI] [PubMed] [Google Scholar]
  23. Visvader J. E., Crossley M., Hill J., Orkin S. H., Adams J. M. The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line. Mol Cell Biol. 1995 Feb;15(2):634–641. doi: 10.1128/mcb.15.2.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whitelaw E., Tsai S. F., Hogben P., Orkin S. H. Regulated expression of globin chains and the erythroid transcription factor GATA-1 during erythropoiesis in the developing mouse. Mol Cell Biol. 1990 Dec;10(12):6596–6606. doi: 10.1128/mcb.10.12.6596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yomogida K., Ohtani H., Harigae H., Ito E., Nishimune Y., Engel J. D., Yamamoto M. Developmental stage- and spermatogenic cycle-specific expression of transcription factor GATA-1 in mouse Sertoli cells. Development. 1994 Jul;120(7):1759–1766. doi: 10.1242/dev.120.7.1759. [DOI] [PubMed] [Google Scholar]

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