Regulation of hematopoietic cell differentiation by Mediator transcriptional coregulator complex
Project/Area Number |
23790623
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Laboratory medicine
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Research Institution | Kobe University |
Principal Investigator |
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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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)
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Keywords | MED1 / 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.
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Report
(4 results)
Research Products
(17 results)
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[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
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Journal Title
Genes to cells
Volume: 19
Issue: 1
Pages: 28-51
DOI
Related Report
Peer Reviewed / Open Access
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[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
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[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
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[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
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[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
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[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
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[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
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[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
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