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Regulation of hematopoietic cell differentiation by Mediator transcriptional coregulator complex

Research Project

Project/Area Number 23790623
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Laboratory medicine
Research InstitutionKobe University

Principal Investigator

URAHAMA Norinaga  神戸大学, 保健学研究科, 研究員 (40403208)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMED1 / Mediator / GATA1 / CCAR1 / CoCoA / メディエーター転写複合体 / 赤芽球分化 / K562 / 転写メディエーター / MED1/TRAP220 / 核内シグナル経路
Research Abstract

The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. An N-terminal fragment of MED1, which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1-602)-interacting coactivator CCAR1, CoCoA, and MED1(681-715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription. Recombinant GATA1, CCAR1, CoCoA, and MED1(1-602) formed a complex in vitro, and GATA1, CCAR1, CoCoA, and MED1 were recruited to the gamma-globin promoter during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function.2014

    • Author(s)
      Mizuta S, Minami T, Fujita H, Kaminaga C, Matsui K, Ishino R, Fujita A, Oda K, Kawai A, Hasegawa N, Urahama N, Roeder RG, Ito M
    • Journal Title

      Genes to cells

      Volume: 19 Issue: 1 Pages: 28-51

    • DOI

      10.1111/gtc.12104

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter.2013

    • Author(s)
      Matsui K. Oda K, Mizuta S, Ishino R, Urahama N, Hasegawa N, Roeder RG, Ito M
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 440 Issue: 1 Pages: 184-189

    • DOI

      10.1016/j.bbrc.2013.09.061

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells2012

    • Author(s)
      Hasegawa N, Sumitomo A, Fujita A
    • Journal Title

      Molecular and Cellular Biology

      Volume: 32 Issue: 8 Pages: 1483-1495

    • DOI

      10.1128/mcb.05245-11

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] CCAR1/CoCoA-mediated Mediator recruitment indicates novel pathway for GATA1 action in erythropoiesis2012

    • Author(s)
      S. Mizuta, C. Kaminaga, H. Fujita, K. Matsui, R. Ishino, K. Oda, A. Fujita, Kubota, N. Urahama, M. Ito
    • Organizer
      第74回日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 赤芽球分化を誘導するコアクチベーターCCAR1とCoCoAの造血組織における特異的発現2012

    • Author(s)
      藤田陽加、水田駿平、神永千尋、織田華澄、松井啓治、森本由紀、畑ともみ、池端夕莉、浦浜憲永、伊藤光宏
    • Organizer
      第74回日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] CCAR1/CoCoA-mediated recruitment of the Mediator indicates a novel pathway for GATA1 action in erythropoiesis2012

    • Author(s)
      S. Mizuta, H. Fujita, C. Kaminaga, T. Minami, K Matsui, R. Ishino, A. Fujita, K. Oda, N. Urahama, R.G. Roeder, M. Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Increased sensitivity to insulin at obese stress in mice with defective MED1 nuclear receptor recognition motifs2012

    • Author(s)
      N. Kubota, K. Matsui, Y. Morimoto, Y. Hirohata, N. Hasegawa, R. Ishino, S. Mizuta, A. Fujita, N. Urahama, R.G. Roeder, M. Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Mediator subunit MED1 is a T3-dependent coactivator on nTRE of the TSHβpromoter2012

    • Author(s)
      K. Matsui, K. Oda, T. Hata, Sh. Mizuta, Y. Hirohata, R. Ishino, N. Urahama, R.G. Roeder, M. Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] CCAR1/CoCoA-mediated Mediator recruitment indicates novel pathway for GATA1 action in erythropoiesis.2012

    • Author(s)
      Shumpei Mizuta, Chihiro Kaminaga, Haruka Fujita, Keiji Matsui, Ruri Ishino, Kasumi Oda, Azusa Fujita, Nana Kubota, Norinaga Urahama, Mitsuhiro Ito
    • Organizer
      第74回日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] CCAR1/CoCoA-mediated recruitment of the Mediator indicates a novel pathway for GATA1 action in erythropoiesis.2012

    • Author(s)
      Shumpei Mizuta, Haruka Fujita, Chihiro Kaminaga, Tomoya Minami, Keiji Matsui, Ruri Ishino, Azusa Fujita, Kasumi Oda, Norinaga Urahama, Robert G. Roeder, Mitsuhiro Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Increased sensitivity to insulin at obese stress in mice with defective MED1 nuclear receptor recognition motifs.2012

    • Author(s)
      Nana Kubota, Keiji Matsui, Yuki Morimoto, Yuko Hirohata, Natsumi Hasegawa, Ruri Ishino, Shumpei Mizuta, Azusa Fujita, Norinaga Urahama, Robert G. Roeder, Mitsuhiro Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Mediator subunit MED1 is a T3-dependent coactivator on nTRE of the TSHβ promoter.2012

    • Author(s)
      Keiji Matsui, Kasumi Oda, Tomomi Hata, Shumpei Mizuta, Yuko Hirohata, Ruri Ishino, Norinaga Urahama, Robert G. Roeder, Mitsuhiro Ito
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] VDR-mediated osteopontin transcription plays crucial role in hematopoietic niche in concert with FGF72011

    • Author(s)
      R. Ishino, K. Matsui, A. Sumitomo, K. Inoue, K. Minami, S. Yamagishi, S. Mizuta, O. Horie, N. Urahama and M. Ito
    • Organizer
      EMBO Conference
    • Place of Presentation
      Nuclear Receptors, Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] GATA1特異的転写共役因子MED1を介する赤芽球分化における核内シグナル副経路の存在2011

    • Author(s)
      水田駿平、南智也、神永千尋、織田華澄、藤田陽加、松井啓治、石野瑠璃、住友明子、浦浜憲永、伊藤光宏
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] CoCoA/CCAR1 pair-mediated recruitment of Mediator complex indicates novel pathway for the function of GATA1 in erythroid differentiation2011

    • Author(s)
      C. Kaminaga, S. Mizuta, T. Minami, K. Oda, H. Fujita, K. Matsui, R. Ishino, A. Sumitomo, N. Urahama, M. Ito
    • Organizer
      53rd Annual Meeting of the American Society of Hematology
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] VDR-mediated osteopontin transcription plays crucial role in hematopoietic niche in concert with FGF72011

    • Author(s)
      R. Ishino, K. Matsui, A. Sumitomo, K. Inoue, K. Minami, S. Yamagishi, S. Mizuta, O. Horie, N. Urahama and M. Ito
    • Organizer
      EMBO Conference, Nuclear Receptors
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www2.kobe-u.ac.jp/~itomi/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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