Molecular role for Geminin in maintaining cardiac muscles

• Project/Area Number: 25670096
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hiroshima University
• Principal Investigator: TAKIHARA Yoshihiro 広島大学, 原爆放射線医科学研究所, 教授 (60226967)
• Co-Investigator(Kenkyū-buntansha): YASUNAGA Shin'ichiro 広島大学, 原爆放射線医科学研究所, 准教授 (50336111) ; OHNO Yoshinori 広島大学, 原爆放射線医科学研究所, 助教 (10548986) ; SHIRAI Manabu 独立行政法人国立循環器病研究センター, 研究所, 室長 (70294121)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ポリコーム遺伝子群 / Geminin / 心筋 / 心臓発生 / 心筋維持 / 維持 / ポリコーム複合体1

Outline of Final Research Achievements

Polycomb-group of (PcG) genes maintain expression of Nkx2.5 gene, a developmental regulator for cardiac development and further act as an E3 ubiquitin ligase for Geminin. On the other hand, overexpression of Rae28 and Pcgf5 deficiency gave rise to dilated cardiomyopathy. Thus, PcG genes are not only involved in cardiac development but also in maintenance of cardiac muscle. We visualized a Geminin molecule by generating Geminin-EYFP knock-in mice. Curiously, we identified cardiac muscles with high Geminin expression in the adult, indicating that these are corresponding with cycling cardiac muscles or cardiac stem cells.

Research Products

• [Journal Article] Transcription of the Geminin gene is regulated by a negative-feedback loop. (2014)
  • Author(s): Ohno, Y., Saeki, K., Yasunaga, S., Kurogi. T., Suzuki-Takedachi, K., Shirai, M., Mihara K., Yoshida, K., Voncken J. W, Ohtsubo, M. & Takihara Y.
  • Journal Title: Mol. Biol. Cel Volume: 25(8) Issue: 8 Pages: 1374-1383
  • DOI: 10.1091/mbc.e13-09-0534
  • Peer Reviewed / Open Access
• [Presentation] Functional roles of Polycomb Ring Finger 5 (Pcgf5) in the heart of adult mice. (2014)
  • Author(s): Shirai, M., Otani, K., Tsuchimochi, H., Takihara, Y., Morisaki, T.
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Molecular role for Geminin in governing hematopoietic stem cell activity (2014)
  • Author(s): Takihara, Y.
  • Organizer: Views into nuclear function: A See Drug Workshop
  • Place of Presentation: Patras, Greece
  • Year and Date: 2014-09-11 – 2014-09-13
  • Invited
• [Presentation] Functional analysis of Pcgf5 (Polycomb ring finger 5) in developing heart (2013)
  • Author(s): Shirai, M.
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸