Functional analysis of Polycomb group proteins in adult heart

• Project/Area Number: 15K09149
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Shirai Manabu 国立研究開発法人国立循環器病研究センター, 創薬オミックス解析センター, 室長 (70294121)
• Co-Investigator(Renkei-kenkyūsha): MORISKI TAKAYUKI 国立循環器病研究センター, 研究所, 部長 (30174410) ; MORISKI HIROKO 国立循環器病研究センター, 研究所, 室長 (40311451)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ポリコーム遺伝子 / 心筋細胞 / 恒常性維持

Outline of Final Research Achievements

To understand the molecular mechanisms of Polycomb group (PcG) proteins in maintaining the cardiac functions, we analyzed Pcgf5 (PcG ring finger 5) functions at adult stage. As reported previously, Pcgf5 formed PRC1.5 complex with Ring1b and RYBP in adult mouse left ventricle (LV). We also found casein kinase 2 alpha 1 (CK2α1) and histone deacetylase 2 (HDAC2) associated with Pcgf5 and other PRC1.5 components. In several phosphoproteins, significant alterations were observed in young and aged Pcgf5-deficient LV. We also compared gene expressions in young and aged LV by RNA-seq analysis and defined specific expression changes in aged Pcgf5-deleted LV. These findings revealed that Pcgf5 plays a pivotal role in maintaining the cardiac function in aged mice.

Research Products

• [Presentation] 成体心臓の機能維持に対するポリコーム遺伝子Pcgf5（Polycomb ring finger 5）の機能解析 (2017)
  • Author(s): 白井 学、錦織 充広、若林 真樹、高橋 篤、金 美花、大谷 健太郎、土持 裕胤、瀧原 義宏、森崎 隆幸、南野 直人
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] Functional analysis of Polycomb repressive complex 1.5 (PRC1.5) in adult mouse heart. (2016)
  • Author(s): Shirai, M., Kim, M., Tsuchimochi, H., Otani, K., Takihara, Y., and Morisaki, T.
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-11-29
• [Presentation] Functional analysis of Polycomb ring finger 5 (Pcgf5) in the heart of adult mice. (2015)
  • Author(s): Shirai, M., Kim, M., Otani, K., Tsuchimochi, H., Takihara, Y., and Morisaki, T.
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Book] Etiology and Morphogenesis of Congenital Heart Disease (2016)
  • Author(s): 編集者 Toshio Nakanishi、Roger R. Markwald、 H. Scott Baldwin、Bradley B. Keller、 Deepak Srivastava、Hiroyuki Yamagishi
  • Total Pages: 383
  • Publisher: Springer