Development of an epigenome-editing technology for inducing cancer epimutations in mice

• Project/Area Number: 15K20888
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science; Tumor biology
• Research Institution: University of Tsukuba
• Principal Investigator: ISEKI Hiroyoshi 筑波大学, 国際統合睡眠医科学研究機構, 助教 (50433652)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エピゲノム編集 / CRISPR/Cas9 / lncRNA / がん / エピゲノム変異モデルマウス

Outline of Final Research Achievements

In this study, we attempted to develop an epigenome-editing technology by applying a CRISPR/Cas9 system and epigenome-modifying enzyme-scaffold proteins and lncRNAs. We first generated a functional small dCas9 mutant by deleting the N-terminal half of the dCas9 protein. Next, we developed an epigenome-editing system with epigenome-modifyling enzyme-scaffold proteins.We also identified a candidate epigenome-modifying enzyme-scaffold lncRNA.

Research Products

• [Journal Article] Germline recombination in a novel Cre transgenic line, Prl3b1-cre mouse. (2016)
  • Author(s): Al-Soudy AS, Hiromori Y, Mizuno S, Hasegawa Y, Shawki HH, Katoh MC, Basha WA, Ibrahim AE, El-Shemy HA, Iseki Hi, Yoshiki A, Nagase H, Nakanishi T, Takahashi S, Oishi H, Sugiyama F.
  • Journal Title: Genesis. Volume: 54(7) Issue: 7 Pages: 389-97
  • DOI: 10.1002/dvg.22944
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Generation of CRISPR/Cas9-mediated bicistronic knock-in <i>ins1-cre</i> driver mice (2016)
  • Author(s): Yoshikazu Hasegawa, Yoshikazu Hoshino, Abdelaziz E. Ibrahim, Kanako Kato, Yoko Daitoku1, Yoko Tanimoto, Yoshihisa Ikeda, Hisashi Oishi, Satoru Takahashi, Atsushi Yoshiki, Ken-ichi Yagami, Hiroyoshi Iseki, Seiya Mizuno, Fumihiro Sugiyama
  • Journal Title: Experimental Animals Volume: 65 Issue: 3 Pages: 319-327
  • DOI: 10.1538/expanim.16-0016
  • NAID: 130006882371
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Combined overexpression of JARID2, PRDM14, ESRRB, and SALL4A dramatically improves efficiency and kinetics of reprogramming to induced pluripotent stem cells. (2016)
  • Author(s): Iseki H, Nakachi Y, Hishida T, Yamashita-Sugahara Y, Hirasaki M, Ueda A, Tanimoto Y, Iijima S, Sugiyama F, Yagami K, Takahashi S, Okuda A, Okazaki Y
  • Journal Title: Stem Cells Volume: 34 Issue: 2 Pages: 322-333
  • DOI: 10.1002/stem.2243
  • Peer Reviewed
• [Presentation] Identification of a causative gene involved in resistance of lymphoma cells to rat parvovirus oncolytic infection by a genome-wide DNA methylation analysis (2016)
  • Author(s): 伊関 大敬、今野 裕士、奥泉 久人、高橋 智、八神 健一、杉山 文博
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市西区みなとみらい一丁目1番1号 パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] Jarid2過剰発現による効率的なiPS細胞誘導 (2016)
  • Author(s): 伊関 大敬、仲地 豊、菱田 友昭、菅原 泉、谷本 陽子、飯島 沙織、杉山 文博、八神 健一、高橋 智、奥田 晶彦、岡崎 康司
  • Organizer: 第62回日本実験動物学会総会
  • Place of Presentation: 京都府京都市南区東九条下殿田町70番地 京都テルサ
  • Year and Date: 2016-05-28