Elucidation of epigenetic transcriptional regulation in germ cell differentiation

• Project/Area Number: 24791662
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: NISHIO Hidenori 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (10621063)
• Research Collaborator: KOHRI Kenjiro ; HAYASHI Yutaro ; KOJIMA Yoshiyuki ; MIZUNO Kentaro ; KUROKAWA Satoshi ; KAMISAWA Hideyuki ; MORITOKI Yoshinobu
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 精子幹細胞 / ヒストン修飾 / 脱メチル化 / エピジェネティクス

Outline of Final Research Achievements

In present study, the aim is to elucidate the mechanism underlying gonocyte transformation to spermatogonial stem cells during spermatogenesis. Kdm5a expression was significantly higher at 9 days postpartum in the undescended testes of experimentally induced cryptorchid model rats than in the normal testes. Since Kdm5a regulates histone H3K4me2/me3 demethylation, H3K4me3/me2 expression levels were decreased in the undescended testes. Moreover, the expression of genes related to spermatogonial stem cell development was induced in spermatogonial cells over expressing Kdm5a. Thus, Kdm5a is likely involved in the transformation of gonocytes into spermatogonial stem cells by transcriptional regulation of specific genes via H3K4 histone modification. This is the first report of epigenetic analysis of germ cell differentiation during early spermatogenesis.

Research Products

• [Journal Article] Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes (2014)
  • Author(s): Nishio H, Hayashi Y, Moritoki Y, Kamisawa H, Mizuno K, Kojima Y, Kohri K
  • Journal Title: J Urol Volume: 191 Issue: 5S Pages: 1564-72
  • DOI: 10.1016/j.juro.2013.10.071
  • Peer Reviewed
• [Presentation] 停留精巣モデルを用いた精子幹細胞分化のエピジェネティックな遺伝子発現制御機構の解明 (2014)
  • Author(s): 西尾英紀、水野健太郎、最上徹、林祐太郎
  • Organizer: 第23回日本小児泌尿器科学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-07-09 – 2014-07-11
• [Presentation] ヒストン修飾酵素Kdm5aを介した精子幹細胞分化のエピジェネティック制御機構の解明 (2014)
  • Author(s): 西尾英紀、水野健太郎、神沢英幸、守時良演、最上徹、岩月正一郎、梅本幸裕、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 日本アンドロロジー学会 第33回学術大会
  • Place of Presentation: 軽井沢プリンスホテルウエスト（長野県・軽井沢）
  • Year and Date: 2014-06-12 – 2014-06-13
• [Presentation] Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes (2014)
  • Author(s): Hidenori Nishio, Yutaro Hayashi, Yoshinobu Moritoki, Yasuhiro Shibata, Hideyuki Kamisawa, Satoshi Kurokawa, Akihiro Nakane, Kentaro Mizuno, Toshiki Kato, Tetsuji Maruyama, Yoshiyuki Kojima, Kenjiro Kohri
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orlando(USA)
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 精子幹細胞におけるヒストンタンパクH3K4の脱メチル化酵素であるKdm5a 遺伝子の機能解析 (2014)
  • Author(s): 西尾英紀、水野健太郎、神沢英幸、守時良演、坂倉毅、林祐太郎、郡健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 精子幹細胞におけるヒストンタンパクH3K4の脱メチル化酵素であるKdm5a遺伝子の機能解析 (2014)
  • Author(s): 西尾 英紀、水野 健太郎、神沢 英幸、守時 良演、坂倉 毅、林 祐太郎、郡 健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes (2014)
  • Author(s): Nishio Hidenori, Hayashi Yutaro, Moritoki Yoshinobu, Kamisawa Hideyuki, Kurokawa Satoshi, Nakane Akihiro, Mizuno Kentaro, Maruyama Tetsuji, Kojima Yoshiyuki, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2014
  • Place of Presentation: Orange County Convention Center (Orlando,USA)
• [Presentation] Jarid1a regulates early stage spermatogenesis by demethylating histone H3 lysine 4 (2013)
  • Author(s): Nishio Hidenori, Mizuno Kentaro, Kurokawa Satoshi, Kamisawa Hideyuki, Imura Makoto, Moritoki Yoshinobu, Shibata Yasuhiro, Nakane Akihiro, Kato Toshiki, Maruyama Tetsuji, Kojima Yoshiyuki, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: The Society for Pediatric Urology 61th Annual Meeting
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] Evaluation of transcriptional regulation by histone H3K4 methylation (2012)
  • Author(s): 西尾英紀
  • Organizer: American Urological Association Annual Meeting 2012
  • Place of Presentation: Atlanta(USA)