Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Dec 5;92(25):11598–11602. doi: 10.1073/pnas.92.25.11598

Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor.

R Calligaris 1, S Bottardi 1, S Cogoi 1, I Apezteguia 1, C Santoro 1
PMCID: PMC40449  PMID: 8524811

Abstract

GATA-1 is a zinc-finger transcription factor that plays a critical role in the normal development of hematopoietic cell lineages. In human and murine erythroid cells a previously undescribed 40-kDa protein is detected with GATA-1-specific antibodies. We show that the 40-kDa GATA-1 (GATA-1s) is produced by the use of an internal AUG initiation codon in the GATA-1 transcript. The GATA-1 proteins share identical binding activity and form heterodimers in erythroleukemic cells but differ in their transactivation potential and in their expression in developing mouse embryos.

Full text

PDF
11598

Images in this article

11599Fig. 1
on p.11599
11600Fig. 2
on p.11600
11600Fig. 3
on p.11600
11601Fig. 4
on p.11601
11601Fig. 5
on p.11601
11601Fig. 6
on p.11601

Selected References

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

  1. Apezteguia I., Calligaris R., Bottardi S., Santoro C. Expression, purification, and functional characterization of the two zinc-finger domain of the human GATA-1. Protein Expr Purif. 1994 Dec;5(6):541–546. doi: 10.1006/prep.1994.1074. [DOI] [PubMed] [Google Scholar]
  2. Crossley M., Orkin S. H. Phosphorylation of the erythroid transcription factor GATA-1. J Biol Chem. 1994 Jun 17;269(24):16589–16596. [PubMed] [Google Scholar]
  3. Del Sal G., Manfioletti G., Gustincich S., Ruaro E., Schneider C. New lambda and plasmid vectors for expression cloning in mammalian cells. Biotechniques. 1994 Jan;16(1):134–138. [PubMed] [Google Scholar]
  4. Delmas V., Laoide B. M., Masquilier D., de Groot R. P., Foulkes N. S., Sassone-Corsi P. Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators with opposite functions. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4226–4230. doi: 10.1073/pnas.89.10.4226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hann S. R., Dixit M., Sears R. C., Sealy L. The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site. Genes Dev. 1994 Oct 15;8(20):2441–2452. doi: 10.1101/gad.8.20.2441. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Kluxen F. W., Lübbert H. Maximal expression of recombinant cDNAs in COS cells for use in expression cloning. Anal Biochem. 1993 Feb 1;208(2):352–356. doi: 10.1006/abio.1993.1060. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  12. Kulessa H., Frampton J., Graf T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev. 1995 May 15;9(10):1250–1262. doi: 10.1101/gad.9.10.1250. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Merika M., Orkin S. H. Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF. Mol Cell Biol. 1995 May;15(5):2437–2447. doi: 10.1128/mcb.15.5.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Ossipow V., Descombes P., Schibler U. CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8219–8223. doi: 10.1073/pnas.90.17.8219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peabody D. S. Translation initiation at non-AUG triplets in mammalian cells. J Biol Chem. 1989 Mar 25;264(9):5031–5035. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schreiber E., Tobler A., Malipiero U., Schaffner W., Fontana A. cDNA cloning of human N-Oct3, a nervous-system specific POU domain transcription factor binding to the octamer DNA motif. Nucleic Acids Res. 1993 Jan 25;21(2):253–258. doi: 10.1093/nar/21.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schöler H. R., Ruppert S., Suzuki N., Chowdhury K., Gruss P. New type of POU domain in germ line-specific protein Oct-4. Nature. 1990 Mar 29;344(6265):435–439. doi: 10.1038/344435a0. [DOI] [PubMed] [Google Scholar]
  24. Steger D. J., Hecht J. H., Mellon P. L. GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Mol Cell Biol. 1994 Aug;14(8):5592–5602. doi: 10.1128/mcb.14.8.5592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Voss J. W., Yao T. P., Rosenfeld M. G. Alternative translation initiation site usage results in two structurally distinct forms of Pit-1. J Biol Chem. 1991 Jul 15;266(20):12832–12835. [PubMed] [Google Scholar]
  27. Weiss M. J., Keller G., Orkin S. H. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes Dev. 1994 May 15;8(10):1184–1197. doi: 10.1101/gad.8.10.1184. [DOI] [PubMed] [Google Scholar]
  28. Yang H. Y., Evans T. Distinct roles for the two cGATA-1 finger domains. Mol Cell Biol. 1992 Oct;12(10):4562–4570. doi: 10.1128/mcb.12.10.4562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yang H. Y., Evans T. Homotypic interactions of chicken GATA-1 can mediate transcriptional activation. Mol Cell Biol. 1995 Mar;15(3):1353–1363. doi: 10.1128/mcb.15.3.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Zon L. I., Yamaguchi Y., Yee K., Albee E. A., Kimura A., Bennett J. C., Orkin S. H., Ackerman S. J. Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. Blood. 1993 Jun 15;81(12):3234–3241. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES