Alteration of DNA binding specificity of Oct3/4 in nucleostemin knock out ESC
| Project/Area Number |
17K15605
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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 |
General medical chemistry
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| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition (2018)
Saitama Medical University (2017) |
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Principal Investigator |
Asaka Masamitsu 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 霊長類医科学研究センター, プロジェクト研究員 (60572865)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ES細胞 / Nucleostemin / Oct3/4 / ChIP-seq / Oct4 / 発現制御 |
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| Outline of Final Research Achievements |
Nucleostemin (NS) is a nucleolar GTP-binding protein that is expressed in various cancer cells and stem cells including embryonic stem cells (ESCs). We have previously demonstrated that knockout of NS resulted in the trophectodermal differentiation, although Oct3/4, one of the transcription factor that repress trophectodermal differentiation, is expressed in NS knockout ESCs. Therefore, we hypothesized that DNA binding ability of Oct3/4 is impaired in NS knockout ESCs.
To address this, we carried out ChIP-seq analyses using NS knockout ESCs, and found that recognition sequence of Oct3/4 was altered in NS knockout ESCs compared with that in normal ESCs. We also revealed that overexpression of Nanog or Esrrb recues the DNA binding ability of Oct3/4 in NS knockdown ESCs.
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| Academic Significance and Societal Importance of the Research Achievements |
ES細胞は、外・中・内胚葉といった3胚葉全ての分化を達成できるが、胎盤等の胚体外組織の元となる栄養外胚葉へと変換する能力は、本来失われている能力である。Nucleostemin遺伝子欠損によるES細胞の栄養外胚葉への変換は、通常の発生とは逆であり、極めて謎である。従って、本研究成果がリプログラミングの研究分野に対して極めて大きなインパクトを与えると考えられる。また、Nucleosteminは、がん細胞でも高発現しているので、本研究からの成果は、がん研究分野に対しても影響を与えるのではないかと期待される。
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Identification of the coiled-coil domain as an essential Mbd3 element for preserving lineage commitment potential of embryonic stem cells2018
Author(s)
Masataka Hirasaki, Atsushi Ueda, Masamitsu N. Asaka, Kousuke Uranishi, Ayumu Suzuki, Masakazu Kohda, Yosuke Mizuno, Yasushi Okazaki, Masazumi Nishimoto, Jafar Sharif, Haruhiko Koseki, Akihiko Okuda
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Journal Title
Stem Cells
Volume: 印刷中
Issue: 9
Pages: 1355-1367
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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