Nutrition-dependent regulation of Nodal gene by a novel histone O-GlcNAc modification

• Project/Area Number: 17K15391
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: Waseda University
• Principal Investigator: Arai Daisuke 早稲田大学, 理工学術院, 講師(任期付) (20624951)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: エピジェネティクス / Nodal / ヒストン修飾 / 発現制御

Outline of Final Research Achievements

Nodal gene plays quite important roles in embryonic development. In this project, we studied regulatory mechanisms of Nodal gene expression, focusing on epigenetics and nutrition. We identified the glucose-responsive histone modification (H2AS40-Gc) on ERE, the regulatory region for Nodal gene. On the other hand, expression level of Nodal in mouse embryonic stem cells was not affected by glucose concentration in the culture medium. Besides, we identified a functional transcription factor binding motif, as well as a target region for epigenetic repression, in ERE.

Academic Significance and Societal Importance of the Research Achievements

Nodal遺伝子の発現異常は先天性疾患やガンの悪性化の原因となるため、制御機構の解明は生物学的にも医学的にも重要な課題である。本研究成果はエピジェネティクスの観点からNodal遺伝子の発現制御と栄養・代謝との関係を示唆しており、栄養環境と分化・発生やガンの悪性化の関係を解明する手がかりになりうる。また、ゲノム編集やエピゲノム編集を駆使することにより新たな知見が得られ、制御機構の全容解明に近づくことができた。

Research Products

• [Journal Article] Sameuramide A, a new cyclic depsipeptide isolated from an ascidian of the family Didemnidae. (2018)
  • Author(s): Machida K, Arai D, Katsumata R, Otsuka S, Yamashita JK, Ye T, Tang S, Fusetani N, Nakao Y
  • Journal Title: Bioorg. Med. Chem. Volume: 26 Issue: 13 Pages: 3852-3857
  • DOI: 10.1016/j.bmc.2018.06.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Kakeromamide A, a new cyclic pentapeptide inducing astrocyte differentiation isolated from the marine cyanobacterium (2018)
  • Author(s): Nakamura F, Maejima H, Kawamura M, Arai D, Okino T, Zhao M, Ye T, Lee J, Chang Y-T, Fusetan N, Nakao Y
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: - Issue: 12 Pages: 2206-2209
  • DOI: 10.1016/j.bmcl.2018.04.067
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Halistanol sulfates I and J, new SIRT1?3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria (2017)
  • Author(s): Nakamura Fumiaki、Kudo Norio、Tomachi Yuki、Nakata Akiko、Takemoto Misao、Ito Akihiro、Tabei Hodaka、Arai Daisuke、de Voogd Nicole、Yoshida Minoru、Nakao Yoichi、Fusetani Nobuhiro
  • Journal Title: The Journal of Antibiotics Volume: 71 Issue: 2 Pages: 273-278
  • DOI: 10.1038/ja.2017.145
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A quantitative shRNA screen identifies ATP1A1 as a gene that regulates cytotoxicity by aurilide B (2017)
  • Author(s): Takase Shohei、Kurokawa Rumi、Arai Daisuke、Kanemoto Kanto Kind、Okino Tatsufumi、Nakao Yoichi、Kushiro Tetsuo、Yoshida Minoru、Matsumoto Ken
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-017-02016-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Marine Natural Products that Control a Specific Set of Histone Modifications (2019)
  • Author(s): Daisuke Arai
  • Organizer: XVI MaNaPro & XI ECMNP, 2019
  • Int'l Joint Research