| Project/Area Number |
15K06952
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
WATANABE KAZUHIDE 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 上級研究員 (40749397)
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| Co-Investigator(Kenkyū-buntansha) |
須田 年生 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
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| Research Collaborator |
Dai Xing University of California, Irvine
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | EMT / TGFbeta / ZEB1 / CAGE / ATAC-seq / chromatin states / transcription factor / epithelial cell / クロマチン / 転写因子 / 遺伝子発現 / OVOL2 / MET / Transcriptomics / Epigenomics / Systems biology / RNA-seq / systems biology |
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| Outline of Final Research Achievements |
In this study, we explored how the gene expression and chromatin status are controlled during epithelial-mesenchymal transition (EMT). In EMT, a cell loses epithelial (E) phenotype and simultaneously acquires mesenchymal (M) phenotype. Our study discovered that the transcription factor ZEB1 plays an important role in controlling reciprocal regulation of E and M phenotypes. As a molecular mechanism, ZEB1 induces closed chromatin states at major E gene loci, while M gene loci are categorized into ZEB1-dependent and independent groups. We constructed a mathematical model based on a hypothesis that "reciprocal changes in E and M genes during EMT are regulated by a ZEB1-TGFbeta positive feedback loop" and succeeded to predict gene expresion changes in EMT.
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