2013 Fiscal Year Final Research Report
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 |
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| Research Field |
Laboratory medicine
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | MED1 / Mediator / GATA1 / CCAR1 / CoCoA |
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| 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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[Journal Article] CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function2014
Author(s)
S. Mizuta, T. Minami, H. Fujita, C. Kaminaga, K. Matsui, R. Ishino, A. Fujita, K. Oda, A. Kawai, N. Hasegawa, N. Urahama, R. G. Roeder, M. Ito
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Journal Title
Genes Cells
Volume: 19
Pages: 28-51
DOI
Peer Reviewed
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[Journal Article] Mediator subunits MED1 and MED24 cooperatively contribute to pubertal mammary gland development and growth of breast carcinoma cells2012
Author(s)
N. Hasegawa, A. Sumitomo, A. Fujita, N. Aritome, S. Mizuta, K. Matsui, R. Ishino, K. Inoue, N. Urahama, J. Nose, T. Mukohara, S. Kamoshida, R. G. Roeder, Ito
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Journal Title
Mol. Cell. Biol
Volume: 32
Pages: 1483-1495
DOI
Peer Reviewed
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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
Year and Date
20121211-14
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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
Year and Date
20121211-14
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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
Year and Date
20111210-13
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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
Year and Date
20110916-20
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