Study on chromosome architecture and regulation in germ cell

• Project/Area Number: 26440003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kumamoto University (2016); Keio University (2014-2015)
• Principal Investigator: Kei-ichiro Ishiguro 熊本大学, 発生医学研究所, 准教授 (30508114)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生殖細胞 / 減数分裂 / 胚性幹細胞 / 着床前胚 / 染色体 / 着床前前胚 / ES細胞 / oocyte / 着床前初期胚 / ES 細胞

Outline of Final Research Achievements

ZSCAN4 is expressed specifically in preimplantation embryos in vivo and ES cells in vitro. However, expression patterns of mouse ZSCAN4 in vivo have been largely elusive. We showed that ZSCAN4 proteins are expressed not only in preimplantation embryo but also in adult ovaries and testes. In ovaries, ZSCAN4 proteins were detected in germinal vesicle stage oocytes, indicating that Zscan4 loci are activated during the late stage in meiotic prophase I. Remarkably, ZSCAN4 showed different spatial localization patterns between two distinct GV oocytes, which can be distinguished by global chromatin organization. These spatiotemporal difference in ZSCAN4 localizations correlated with the transition of RNA polymerase II-mediated transcriptional status during GV oocytes maturation. In testes, ZSCAN4 proteins were detected in spermatocytes at late pachytene/diplotene stages and in Sertoli cells. These results suggest that ZSCAN4 may play critical roles during late meiotic prophase in germ cells.

Research Products

• [Int'l Joint Research] Fondazione IRCCS(Italy)
• [Int'l Joint Research] Research Center for/Regenerative Medicine(Italy)
• [Journal Article] Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos (2017)
  • Author(s): Ishiguro K., Nakatake Y., Chikazawa-Nohtomi N., Kimura H., Akiyama T., Oda M., Ko SBH., Ko MSH.
  • Journal Title: In Vitro Cell.Dev.Biol.-Anim. Volume: 53 Issue: 2 Pages: 179-190
  • DOI: 10.1007/s11626-016-0097-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis (2017)
  • Author(s): Ishiguro K., Monti M., Akiyama T., Kimura H., Chikazawa-Nohtomi N., Sakota M., Sato S., Redi CA., Ko SBH., Ko MSH.
  • Journal Title: In Vitro Cell.Dev.Biol.-Anim. Volume: 53 Issue: 2 Pages: 167-178
  • DOI: 10.1007/s11626-016-0096-z
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 減数第一分裂に特異的な染色体分配を制御する新規動原体因子MEIKIN (2015)
  • Author(s): 石黒啓一郎, 金智慧, 渡邊嘉典
  • Journal Title: 実験医学 Volume: 33 Pages: 1427-1431
• [Journal Article] マウスES細胞の染色体安定性を制御するエピゲノム機構 (2015)
  • Author(s): 秋山智彦, 小田真由美, 石黒啓一郎, 洪繁, 洪実
  • Journal Title: 細胞工学 Volume: 34 Pages: 1052-1056
• [Journal Article] MEI4: a central player in the regulation of meiotic DNA double strand break formation in the mouse (2015)
  • Author(s): Kumar R., Ghyselinck N., Ishiguro K., Watanabe Y., Kouznetsova A., Höög C., Strong E., Schimenti J., Daniel K., Toth A., de Massy B.
  • Journal Title: Journal of Cell Science Volume: 128 Pages: 1800-1811
  • DOI: 10.1242/jcs.165464
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Meikin is a conserved regulator of meiosis-I-specific kinetochore function (2015)
  • Author(s): Kim, J., Ishiguro, K., Nambu, A., Akiyoshi, B., Yokobayashi, S., Kagami, A., Ishiguro, T., Pendas, A.M., Takeda, N., Sakakibara, Y., Kitajima, T.S., Tanno, Y., Sakuno, T., and Watanabe, Y.
  • Journal Title: Nature Volume: 517 Issue: 7535 Pages: 466-471
  • DOI: 10.1038/nature14097
  • Peer Reviewed
• [Journal Article] p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex (2014)
  • Author(s): Belzil C., Asada N., Ishiguro K., Nakaya T., Parsons K., Pendolino V., Neumayer G., Mapelli M., Nakatani Y., Sanada K., Nguyen MD.
  • Journal Title: Biology OPEN Volume: 3 Issue: 6 Pages: 475-485
  • DOI: 10.1242/bio.20147807
  • Peer Reviewed / Open Access
• [Presentation] ZSCAN4 is expressed not only in preimplantation embryos but also in adult ovaries and testes (2016)
  • Author(s): Kei-ichiro Ishiguro, Manuela Monti, Tomohiko Akiyama, Hiromi Kimura, Nana Chikazawa-Nohtomi, Miki Sakota, Saeko Sato, Carlo Alberto Redi, Shigeru B.H. Ko, Minoru S.H. Ko
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] Meikin is a conserved regulator of meiosis-I-specific kinetochore function (2014)
  • Author(s): Kim J, Ishiguro K., Nambu A., Sakakibara Y., Kitajima T.S., Watanabe Y.
  • Organizer: 第32回染色体ワークショップ
  • Place of Presentation: 広島廿日市市 安芸グランドホテル
  • Year and Date: 2014-12-15 – 2014-12-17
• [Book] 実験医学 (2015)
  • Author(s): 石黒啓一郎, 金智慧、渡邊嘉典
  • Total Pages: 5
  • Publisher: 羊土社
• [Book] ライフサイエンス新着論文レビュー (2015)
  • Author(s): 石黒啓一郎, 金智慧、渡邊嘉典
  • Total Pages: 6
  • Publisher: 大学共同利用機関法人 情報・システム研究機構ライフサイエンス統合データベースセンター
• [Remarks] 熊本大学発生医学研究所 染色体制御分野 分野紹介
  • URL: http://www.imeg.kumamoto-u.ac.jp/bunya_top/chromosome-biology/seika/
• [Remarks] 慶應義塾大学医学部 システム医学講座
  • URL: http://systemsmedicine.jp/about/