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Cloning and functional analysis of molecules for eosinophil differentiation

Research Project

Project/Area Number 10670959
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

OIKE Yuichi (1999)  School of Medicine, Kumamoto University, Associate Professor, 医学部, 助手

山口 祐司 (1998)  熊本大学, 医学部, 講師 (00220286)

Co-Investigator(Kenkyū-buntansha) 尾池 雄一  熊本大学, 医学部, 助手
YAMAGUCHI Yuji  School of Medicine, Kumamoto University, Assistant Professor (00220286)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsEosinophil / MBP / GATA-1 / GATA-2 / C / EBP / Vasculo-angiogenesis / Gene trap / CBP
Research Abstract

Differentiation of eosinophils from myeloid progenitors is regulated by several different cytokines, including IL-3, GM-CSF and IL-5. However the molecular basis for the commitment of hematopoietic stem cells to the eosinophil lineage remains to be elucidated. We have been characterizing the regulatory regions of genes encoding eosinophil-specific proteins, including eosinophil peroxidase (EPO) Charcot-Leyden crystal (CLC) protein, and eosinophil major basic protein (MBP), to identify transcription factors involved in regulating the commitment and terminal differentiation of myeloid progenitors to the eosinophil lineage.
We demonstarted a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the eosinophilic cell line, HT93A, C/EBPα mRNA expression decreased significantly concomitant with eosinophilic differentiation,whereas C/EBPβ expression was markedly increased. We show that both C/EBPβand GATA-1 can bind simultaneously to the C/EBP- and GATA-1 binding sites in the MBP promoter and that synergistically transactivate the MBP P2 promoter with GATA-1. In addition, we provide evidence that FOG, a cofactor for GATA-binding proteins, may act as a negative cofactor in the eosinophil linegae, unlike its role as a positive cofactor for erythroid and megakaryocyte gene expression.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Oike Y: "Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis"Blood. 93. 2771-2779 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi Y, Nishio H, Kasahara T, Ackerman SJ, Koyanagi H and Suda T: "Model of lineage switching in hemato-poietic development: a new myeloid committed eosinophil cell line (YJ) demonstrates trilineage potential"Leukemia. 12. 1430-1439 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishio K, Suda T, Sawada K-I, Miyamoto T, Koike T and Yamaguchi Y: "Molecular cloning of cDNA encoding human Rab3D whose expression is upregulated with myeloid differentiation"Biochem Biophy Acta. 1444. 283-290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi Y, Ackerman SJ, Minegishi N, Yamamoto M, Suda T: "Mechanisms of transcription in the eosinophils: GATA-1but not GATA-2 transactivates the promoter of granule major basic protein gene"Blood. 91. 3447-3458 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi Y, Nishio H, Kishi K, Ackerman SJ and Suda T: "C/EBPβ and GATA-1 synergistically regulate activity of the eosinphil granule major basic protein promoter: Implication for C/EBPβ activity in eosinophil gene expression"Blood. 94. 1429-1439 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamaguchi Y, Zon LI, Ackerman SJ, Yamamoto M and Suda T: "Forced GATA-1 Expression in the murine myeloid cell line M1: Induction of c-Mp1 expression and megakaryocytic/erythroid differentiation"Blood. 91. 450-457 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Oike Y, Takakura N, Hata A, Kaname T, Akizuki M, Yamaguchi Y, Yasue H, Araki K, Yamamura K-i and Suda T: "Mice homo-zygous for a truncated form of CREB-binding protein exihibit defects in hematopoiesis and vasculo-angiogenesis"Blood. 93. 2771-2779 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuichi Oike: "Mice Homozygous tor a Trun*cter For in it cREB-Binding Protein(CBP)Exlnbip Defects in He**topcies*s and Daecale **ngic genosis"Blood. 93. 2771-2779 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuichi Oike: "Trureat**r CBP protein leads to claecical Rubxnstein-Toybisynd**m pleu*y in mice J**plication for a clnical *epatus mechanism"Hum.Mol.Genet.. 18. 387-396 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yi Yi Myint: "Gromiocyte/vinaroprage clony sti***ting factor and interleutin 3 ccrred osteoprosis in mice with oste*p*rosts nutation"Am.J.Pathol.. 154. 553-566 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toshio Suda: "Heanot*p*ies*s and Aug*o genosis"Int.J.Hematol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamaguchi, Y.,et al: "Forced GATA-1 expression in the murine myeloid cell line M1:Imduction of c-mpl expression and megakaryocytic/erythreid differentiation" BLOOD. 91. 450-457 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamaguchi, Y.,et al.: "Mechanisms of transcription in eosinophis:GATA-1,but not GATA-2,transactivates the promoter of the eosinophil granule major basic protein gene" BLOOD. 91. 3447-3458 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sadat,M.A.,et al.: "GATA-3 binding to an inrerted GATA consensus motif represses gp91R gene expression in eosinophil-commitled HL-60-C15 cells" FEBS Letters. 436. 390-394 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Duan,Y.,et al.: "Expression and function of NJ-1(114/A10),a cell surface protein which in associated with megakaryocytic differentiation" Biochem.Biophys.Res.Commun.253. 401-406 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hamaguchi,I.,et al.: "In vitro hematopietic and endothelial cell development from cells expressiong TEK receptors in murine AGM region" BLOOD. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishio,H.,et al.: "Molecular cloning of cDNA encoding human Rab3D whose expression in up-regulated with myeloid differentiation" Biochimica et Biophysica Acta. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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