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1997 Fiscal Year Final Research Report Summary

Transcription factors regulating the erytnroid and megakaryocytic cell differentiation.

Research Project

Project/Area Number 08670162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionUniversity of Tsukuba (1997)
Tohoku University (1996)

Principal Investigator

MINEGISHI Naoko  University of Tsukuba, Institute of Basic Medicine, Lecturer, 基礎医学系, 講師 (40271895)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Masayuki  University of Tsukuba, Institute of Basic Medicine, Professor, 基礎医学系, 教授 (50166823)
HAYASHI Norio  Tohoku University, School of Medicine, Professor, 医学部, 教授 (00004606)
Project Period (FY) 1996 – 1997
KeywordsGATA-2 / GATA-1 / NF-E2p45 / megakaryoyte / erythrocyte / hematopoietic stem cell / erythropoietin / thrombopoetin
Research Abstract

In the erythroid and megakaryocytic lineage cells, GATA-1 and GATA-2 show overlapping expression. The gene targeting experiments demonstrate that GATA-2 is essential for the hematopoietic stem and progenitor cells while GATA-1 expression is required for the terminal differentiation of both erythrocytes and megakaryocytes. We investigated the gene expression of GATA factors on leukemic cells and the transcriptional regulation of GATA-2 gene. The results are as follows ;
1), GATA-1 and GATA-2 were expressed concomitantly on the leukemic cells with megakaryocytic or erythroid surface markers. GATA-2 mRNA was also detected in the myelogenous leukemia cells without any megakaryocytic or erythroid features. GATA-2 expression in leukemic cells were correlated with the c-kit antigen expression. This finding was consistent with the reports that GATA-2 has distinct functions in hematopoietic stem/progenitor cells.
2), Transcription of mouse GATA-2 gene was found to initiate from two distinct first … More exons, both of which encode entirely untranslated regions, while the remaining five exons are shared by each of the two divergent mRNAs. Reverse transcriptase-polymerase chain reaction analysis revealed that GATA-2 mRNA initiated at the upstream first exon (IS) in Sca-1+/c-kit+hematopoieticprogenitor cells, whereas mRNA initiated at the downstream first exon (IG) is expressed in all tissues and cell lines that express GATA-2. While the structure of the IG exon/promoter shows high similarity to those of the Xenopus and human GATA-2 gene, the IS exon/promoter has not been described previously. Sequences lying between-79 and -61 are found to be critical for the cell type-specific activity of the IS promoter, and the binding of transcription factors to this region were demonstrated.
3), A transgene containing the IS promoter and 6 kbp upstream region diercted expression of a reporter gene recapitulated the GATA-2 expression in aorta-gonads-mesonephros region and in bone marrow cells. Deletion analysis of the upstream region of IS promoter localized a hematopoietic enhancer activity between 3.5 to 2.5 kbp upstream of the IS exon. This region contained one of the DNaseI hypersensitve sites. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Minegishi, N. et al.: "Alternative promoters regulate transcription of the mouse GATA-2 gene." J.Biol.Chem.273. 3625-3634 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minegishi, N. et al.: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells." Int.J.Hematol.65. 239-249 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai, T. et al.: "Regulation of NF-E2 activity in erythroleukemia cell differentiation." J.Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onodera, K. et al.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 94. 4487-4492 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imagawa, S. et al.: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. 89. 1430-1439 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, S.: "Arrest in erythroid cell development by promoter-specific disruption of GATA-1 gene." J.Biol.Chem.272. 12611-12615 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naoko Minegishi, et al.: "Altermative promoter regulate transcriptio of the mouse GATA-2 gene." Journal of Biological Chemistry. 273. 3625-2634 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naoko Minegishi, et al.: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells." International Journal of Hematology. 65. 239-249 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tadashi Nagai, et al.: "Regulation of NF-E2 activity in erythroleukemia cell differentiation." Journal of Biological Chemistry. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ko Onodera, et al.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Procedings of Ntional Academy of Science.USA.94. 4487-4492 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigehiko Imagawa, et al.: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. 891. 430-1439 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoru Takahashi, et al.: "Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene." Journal of Biological Chemistry. 272. 12611-12615 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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