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Analyses of transcription factors related to megakaryocyte differentiation and maturation.

Research Project

Project/Area Number 16390022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionOsaka University

Principal Investigator

DOI Takefumi  Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (00211409)

Co-Investigator(Kenkyū-buntansha) NAKANO Tohru  Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究科, 教授 (00172370)
TAIRA Kazunari  The University of Tokyo, School of Engineering, Professor, 工学系研究科, 教授 (10261778)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsMegakaryocyte / Platelet Factor 4 / FPD / AML / UT7 / GM cell / GATA-1 / AML-1 / ETS-1 / USF / 免疫沈降 / p21 / E-box / クロマチン免疫沈降 / ドミナントネガティブ
Research Abstract

We have previously determined the cis-element that is responsible for the megakaryocyte specific expression of the PF4 gene and the proteins that bind to this element. In this study, we investigated the function of USFs and AML-1 which were involved in these proteins. We found that these transcription factors stimulated the expression of the PF4 gene. We further studied the biological function of AML-1. Although we could detect ETS-1 protein in the transcriptional complex including AML-1, we could not find CBFβ which up-regulated the transcriptional activity of AML-1 in the complex. We next investigated the function of AML-1 for the megakaryocyte differentiation. The knock down experiments of AML-1 by using RNAi revealed that AML-1 promoted the megakaryocyte differentiation and maturation at the early stage of megakaryopoiesis. However, AML-1 repressed the differentiation at the late stage of megakaryopoiesis.
We also investigated the relationship between AML-1 mutations and familial platelet disorder (FPD). The transcriptional activities of AML-1 mutants on the PF4 gene expression were studied. We found that a certain AML-1 mutants not only diminished their own transcriptional activities but also inhibited the transcription by the wild type AML-1. Further analyses revealed that these mutants inhibited the transport of ETS-1 to the nucleus. These results provide us important information for the future approaches to the FPD research.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004

All Journal Article (21 results)

  • [Journal Article] RUNX1 suppression induces megakaryocytic differentiation of UT-7/GM cells2006

    • Author(s)
      Ryohei Nagai
    • Journal Title

      Biochemical and Biophysical Research Communications 345・1

      Pages: 78-84

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of RUNX1 by siRNA in megakaryocytic UT-7/GM cells.2006

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Nucleic Acids Symposium Series No・50

      Pages: 261-262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multipotential differentiation ability of GATA-1-null erythroid-committed cells2006

    • Author(s)
      Kenji Kitajima
    • Journal Title

      Genes & Development 20・6

      Pages: 654-659

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-22006

    • Author(s)
      Kenji Kitajima
    • Journal Title

      Blood 107・5

      Pages: 1857-1863

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] RUNX1 suppression induces megakaryocytic differentiation of UT-7/GM cells2006

    • Author(s)
      Ryohei Nagai
    • Journal Title

      Biochemical and Biophysical Research Communications 345(1)

      Pages: 78-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of RUNX1 by siRNA in megakaryocytic UT-7/GM cells2006

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Nucleic Acids Symposium Series No.50

      Pages: 261-262

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Multipotential differentiation ability of GATA-1-null erythroid-committed cells2006

    • Author(s)
      Kenji Kitajima
    • Journal Title

      Genes & Development 20(6)

      Pages: 654-659

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-22006

    • Author(s)
      Kenji Kitajima
    • Journal Title

      Blood 107(5)

      Pages: 1857-1863

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] RUNX1 suppression induces megakaryocytic differentiation of UT-7/GM cells2006

    • Author(s)
      Ryohei Nagai
    • Journal Title

      Biochemical and Biophysical Research Communications 345

      Pages: 78-84

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of RUNX1 by siRNA in megakaryocytic UT-7/GM cells.2006

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Nucleic Acids Symposium Serries 50

      Pages: 261-262

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multipotential differentiation ability of GATA-1 null erythroid committed cells2006

    • Author(s)
      Kitajima K
    • Journal Title

      Genes & Development 20

      Pages: 654-659

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differential Effects of GATA-1 on Proliferation and Differentiation of Erythroid Lineage Cells2006

    • Author(s)
      Zheng J
    • Journal Title

      Blood 107

      Pages: 520-527

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 巨核球・血小板系列特異的遺伝子発現制御に関与する転写因子群の解析2005

    • Author(s)
      土井 健史
    • Journal Title

      生産と技術 57・1

      Pages: 38-41

    • NAID

      40006607488

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 巨核球・血小板系列の遺伝子発現に閲与する転写因子2005

    • Author(s)
      土井 健史
    • Journal Title

      薬学雑誌 125・9

      Pages: 685-697

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Analyses of transcription factors regulating megakaryocyte-specific gene expression2005

    • Author(s)
      Takefumi Doi
    • Journal Title

      Seisan to Gijutsu 57(1)

      Pages: 38-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transcription Factors Responsible for Megakaryocyte-specific Gene Expression2005

    • Author(s)
      Takefumi Doi
    • Journal Title

      Yakugaku Zasshi 125(9)

      Pages: 685-697

    • NAID

      110004042056

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 巨核球・血小板系列の遺伝子発現に関与する転写因子2005

    • Author(s)
      土井 健史
    • Journal Title

      薬学雑誌 125・9

      Pages: 685-697

    • NAID

      110004042056

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 巨核球・血小板系列特異的遺伝子発現制御に関与する転写因子群の解析2005

    • Author(s)
      土井健史, 岡田欣晃
    • Journal Title

      生産と技術 57・1

      Pages: 38-41

    • NAID

      40006607488

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes2004

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Blood 104・7

      Pages: 2727-2034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes2004

    • Author(s)
      Yoshiaki Okada
    • Journal Title

      Blood 104(7)

      Pages: 2027-2034

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes.2004

    • Author(s)
      Y.Okada, E.Matsuura, Z.Tozuka, R.Nagai, A.Watanabe, K.Matstumoto, K.Yasui, R.W.Jackman, T.Nakano, T.Doi
    • Journal Title

      Blood 104・7

      Pages: 2027-2034

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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