Functional analysis of Zfp281 during early embryogenesis

• Project/Area Number: 18K14717
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Kyushu University
• Principal Investigator: Ishiuchi Takashi 九州大学, 生体防御医学研究所, 助教 (80612100)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胎盤発生 / エピジェネティクス / 転写因子 / ヒストン修飾 / 初期発生

Outline of Final Research Achievements

Proper placental development is essential for mammalian reproduction. However, the molecular mechanisms underlying the placental development is poorly understood. In this study, we identified Zfp281 as a key factor. Zfp281 was preferentially expressed in mouse trophoblast stem (TS) cells in vivo and in vitro, and its expression was down-regulated upon differentiation. Zfp281 knockout mice showed embryonic lethality and severe defects in early placental development. The transcriptome of Zfp281 knockout embryos and TS cells in vitro displayed impaired patterns, suggesting that Zfp281 controls placental development through transcriptional regulation.

Academic Significance and Societal Importance of the Research Achievements

われわれ人を含む有胎盤哺乳類において、胎盤形成は次世代の生命の誕生およびライフサイクルの維持に欠かすことができない。しかしながら、胎盤発生を支持する遺伝子や分子機構の理解はあまりすすんでいない。そこで本研究では、胎盤発生に重要な遺伝子の同定を試み、その結果Zfp281を同定した。Zfp281は転写因子として機能し複数のターゲット遺伝子の発現調節を担うこと、さらに、Zfp281はヒストン修飾を担う分子複合体との相互作用を介してその機能を発揮することが明らかとなった。

Research Products

• [Journal Article] Zfp281 shapes the transcriptome of trophoblast stem cells and is essential for placental development (2019)
  • Author(s): Ishiuchi, T., Ohishi, H., Sato, T., Kamimura, S., Yorino, M., Abe, S., Suzuki, A., Wakayama, T., Suyama, M., Sasaki, H.
  • Journal Title: Cell Reports Volume: 27 Issue: 6 Pages: 1742-1754
  • DOI: 10.1016/j.celrep.2019.04.028
  • Peer Reviewed / Open Access
• [Presentation] Zfp281 shapes the transcriptome of trophoblast stem cells and regulates placental development (2018)
  • Author(s): Takashi Ishiuchi
  • Organizer: 第16回幹細胞シンポジウム
  • Int'l Joint Research
• [Presentation] Zfp281-dependent epigenetic and transcriptional regulation in trophoblast stem cells is essential for placental development (2018)
  • Author(s): Takashi Ishiuchi, Hiroaki Ohishi, Tetsuya Sato, Shusaku Abe, Teruhiko Wakayama, Mikita Suyama, Hiroyuki Sasaki
  • Organizer: 第12回日本エピジェネティクス研究会年会
• [Presentation] Epigenetic and transcription factor-mediated pathways in developmental regulation (2018)
  • Author(s): Takashi Ishiuchi
  • Organizer: IES meeting
  • Int'l Joint Research