Analysis of leukemogenesis caused by disruption of gene regulatory mechanisms mediated by multiple transactivation domains
| Project/Area Number |
24659142
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAMOTO Masayuki 東北大学, 医学(系)研究科(研究院), 教授 (50166823)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Ritsuko 東北大学, 大学院医学系研究科, 教授 (40226262)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 分子腫瘍学 / GATA転写因子 / 遺伝子改変マウス / 白血病 / 転写制御 |
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| Research Abstract |
GATA1 is a transcription factor essential for comprehensive regulation of genes involved in erythroid/megakaryocytic cell differentiation, utilizing two separate transactivation domains (TADs) located in amino(N)- and carboxyl(C)-terminal region of the molecule, respectively. Acute megakaryoblastic leukemia (AMKL) in children with Down syndrome is associated with GATA1 lacking N-TAD. We established transgenic mouse lines expressing mutant GATA1s lacking either N-TAD or C-TAD and analyzed the function of the domains in mice. We found that both N-TAD and C-TAD are important for fetal hematopoiesis. We also found that the disturbed function due to the lack of one TAD could be compensated by the functional enhancement of the other TAD in erythroid cells, whereas lack of N-TAD function could not be compensated in megakaryocytes. These results indicate that a skewed transactivation activity caused by single function of C-TAD is involved in the onset of Down syndrome AMKL.
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Report
(3 results)
Research Products
(52 results)
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[Journal Article] PGC-1 Coactivator Activity is Required for Murine Erythropoiesis2014
Author(s)
Cui S, Tanabe O, Lim K-C, Xu HE, Zhou XE, Lin JD, Shi L, Shimizu R, Schmidt L, Campbell A, Yamamoto M, and Engel JD,
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Journal Title
Mol Cell Biol
Volume: 34
Issue: 11
Pages: 1956-1965
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.2013
Author(s)
Watanabe S, De Zan T, Ishizalki T, Yasuda S, Kamijo H, Yamada D, Aoki T, Kiyonari H, Kaneko H, Shimizu R, Yamamoto M, Goshima G, and, Narummiya S
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Journal Title
Cell Reports
Volume: 5(4)
Issue: 4
Pages: 926-932
DOI
Related Report
Peer Reviewed
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[Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation2013
Author(s)
Suzuki M, Kobayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, Yamamoto M
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Journal Title
Genes Cells
Volume: 18
Issue: 11
Pages: 921-933
DOI
Related Report
Peer Reviewed
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[Journal Article] Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain2013
Author(s)
Mukai HY, Suzuki M, Nagano M, Ohmori S, Otsuki A, Tsuchida K, Moriguchi T, Ohneda K, Shimizu R, Ohneda O, Yamamoto M,
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Journal Title
Genes Cells
Volume: 18
Issue: 10
Pages: 886-898
DOI
Related Report
Peer Reviewed
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[Journal Article] Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome2013
Author(s)
Toki T, Kanezaki R, Kobayashi E, Kaneko H, Suzuki M, Wang R, Terui K, Kanegane H, Maeda M, Endo M, Mizuochi T, Adachi S, Hayashi Y, Yamamoto M, Shimizu R, Ito E.
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Journal Title
Blood
Volume: 121(16)
Issue: 16
Pages: 3181-3184
DOI
Related Report
Peer Reviewed
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[Journal Article] UG4 enhancer-driven GATA-2 and bone morphogenetic protein 4 complementation remedies the CAKUT phenotype in Gata2 hypomorphic mutant mice2012
Author(s)
Ainoya K, Moriguchi T, Ohmori S, Souma T, Takai J, Morita M, Chandler KJ, Mortlock DP, Shimizu R, Engel JD, Lim KC, Yamamoto M.
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Journal Title
Molecular and Cellular Biology
Volume: 32
Issue: 12
Pages: 2312-2322
DOI
Related Report
Peer Reviewed
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