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Regulation of hematopoiesis through a novel nuclear receptor coactivator TRAP/Mediator complex

Research Project

Project/Area Number 16590941
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ITO Mitsuhiro  Kobe University, Hospital, Assistant Professor, 医学部附属病院, 助手 (50362794)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsTranscriptional Mediator / TRAP220 / MED1 / myelomonocytic differentiation / retinoic acid receptor / vitamin D receptor / HL-60細胞 / 増殖・分化・恒常性維持 / 顆粒球分化 / 単球分化 / RNA干渉法
Research Abstract

The TRAP/Mediator complex, the metazoan counterpart of the yeast Mediator complex, is master transcriptional regulatory complex composed of approximately 30 subunits. It was originally isolated as a thyroid hormone receptor (TR)-associated protein (TRAP) complex that mediates TR-activated transcription from DNA templates in vitro and probably acts in vivo after the action of other receptor-interacting coactivators involved in chromatin remodeling. The TRAP220/MED1 subunit of the TRAP/Mediator complex is proposed to act on a variety of major and specific biological events, including growth, differentiation and homeostasis, through physical interaction with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. The functional role of TRAP220/MED1 in nuclear receptor-mediated monopoiesis and granulopoiesis is presented. Since … More TRAP220 knockout mice were mortal before definitive hematopoiesis becomes dominant, the function of TRAP220/MED1 in adult hematopoiesis was mostly unknown. However, these embryos appeared to have normal composition of nucleated erythroid cells. Therefore, the E9.0 yolk sac-derived hematopoietic precursor cells were used to differentiate into definitive hematopoietic colony forming units. The number of monocytic colonies (CFU-M) was significantly lower in knockouts, while the numbers of other colonies (CFU-GEMM, CFU-GM, CFU-G and CFU-E) were comparable. Then, the HL-60 acute promyelocytic leukemia cells were used to elucidate directly and mechanistically the roles of TRAP220/MED1 in RAR- and VDR-dependent differentiation of the hematopoietic precursor cells. Flow cytometric analyses showed that HL-60 cells, wherein TRAP220/MED1 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by ligand stimulation. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells. These results indicated a crucial role of TRAP220/MED1 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis. Less

Report

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

    (21 results)

All 2005 2004

All Journal Article (21 results)

  • [Journal Article] The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation.2005

    • Author(s)
      Urahama, N., 他
    • Journal Title

      Genes Cells 10(12)

      Pages: 1127-1137

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.2005

    • Author(s)
      Yakushijin, K., 他
    • Journal Title

      Kobe J. Med. Sci. 51(4)

      Pages: 55-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome.2005

    • Author(s)
      Yamamoto, K., 他
    • Journal Title

      Cancer Genet. Cytogenet. 162(2)

      Pages: 160-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation.2005

    • Author(s)
      Urahama, N.et al.
    • Journal Title

      Genes Cells 10(12)

      Pages: 1127-1137

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.2005

    • Author(s)
      Yakushijin, K.et al.
    • Journal Title

      Kobe J.Med.Sci. 51(4)

      Pages: 55-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome.2005

    • Author(s)
      Yamamoto, K.et al.
    • Journal Title

      Cancer Genet.Cytogenet. 162(2)

      Pages: 160-165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation.2005

    • Author(s)
      Urahama, N. et al.
    • Journal Title

      Genes Cells 10(12)

      Pages: 1127-1137

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.2005

    • Author(s)
      Yakushijin, K. et al.
    • Journal Title

      Kobe J.Med.Sci. 51(4)

      Pages: 55-65

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome.2005

    • Author(s)
      Yamamoto, K. et al.
    • Journal Title

      Cancer Genet.Cytogenet. 162(2)

      Pages: 160-165

    • Related Report
      2005 Annual Research Report
  • [Journal Article] TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription.2004

    • Author(s)
      Jiang C., 他
    • Journal Title

      J. Biol. Chem. 279(26)

      Pages: 27781-27789

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of casein kinase lepsilon in cytokine-induced granulocytic differentiation.2004

    • Author(s)
      Okamura A., 他
    • Journal Title

      Blood 103(8)

      Pages: 2997-3004

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] An extra X chromosome as a sole abnormality in relapse of an adult acute lymphoblastic leukemia.2004

    • Author(s)
      Yamamoto K., 他
    • Journal Title

      Cancer Genet. Cytogenet. 155(2)

      Pages: 154-155

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Unbalanced translocation der(11)t(11;12)(q23;q13) : a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype.2004

    • Author(s)
      Yamamoto K., 他
    • Journal Title

      Cancer Genet. Cytogenet. 155(1)

      Pages: 67-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription.2004

    • Author(s)
      Jiang, C.et al.
    • Journal Title

      J.Biol.Chem. 279(26)

      Pages: 27781-27789

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of casein kinase lepsilon in cytokine-induced granulocytic differentiation.2004

    • Author(s)
      Okamura, A.et al.
    • Journal Title

      Blood 103(8)

      Pages: 2997-3004

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] An extra X chromosome as a sole abnormality in relapse of an adult acute lymphoblastic leukemia.2004

    • Author(s)
      Yamamoto, K.et al.
    • Journal Title

      Cancer Genet.Cytogenet. 155(2)

      Pages: 154-155

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Unbalanced translocation der(11)t(11;12)(q23;q13) : a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype.2004

    • Author(s)
      Yamamoto, K.et al.
    • Journal Title

      Cancer Genet.Cytogenet. 155(1)

      Pages: 67-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription.2004

    • Author(s)
      Jiang C. 他
    • Journal Title

      J.Biol.Chem. 279(26)

      Pages: 27781-27789

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation.2004

    • Author(s)
      Okamura A. 他
    • Journal Title

      Blood 103(8)

      Pages: 2997-3004

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An extra X chromosome as a sole abnormality in relapse of an adult acute lymphoblastic leukemia.2004

    • Author(s)
      Yamamoto K. 他
    • Journal Title

      Cancer Genet.Cytogenet. 155(2)

      Pages: 154-155

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Unbalanced translocation der(11)t(11;12)(q23;q13) : a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype.2004

    • Author(s)
      Yamamoto K. 他
    • Journal Title

      Cancer Genet.Cytogenet. 155(1)

      Pages: 67-73

    • Related Report
      2004 Annual Research Report

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

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