Chromatin remodeling factor ARIP4 regulates the cardiomyocyte differentiation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Osaka University
• Principal Investigator: TSUCHIYA Megumi 大阪大学, 生命機能研究科, 特任助教(常勤) (00390691)
• Research Collaborator: TAKEUCHI jun ; OGAWA hidesato ; HIRAOKA yasushi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 心筋分化誘導 / 心筋細胞 / クロマチン変換因子

Outline of Final Research Achievements

In this study, we demonstrate that the chromatin remodeling factor, ARIP4 played an essential role for cardiomyocyte differentiation of mouse embryonic stem (ES) cells. The reducing of protein levels of ARIP4 or an ectopic expression of ATPase mutant of ARIP4 suppressed the ES differentiation to the cardiomyocyte. Interestingly, genome-wide analysis clearly showed that ARIP4 mainly localized near the promoter region and the region was inactivated through the ATPase activity of ARIP4. Furthermore, endogenous ARIP4 interacted with p62 in mice embryonic hearts. Since p62 is well known as a selective autophagy receptor, it is suggested that p62 monitors the cellular energy levels and regulates the protein levels of ARIP4 during the cardiomyocyte differentiation. These data strongly suggest that ARIP4 acts as a key regulator for the cardiomyocyte differentiation through the modulation of chromatin structure with monitoring the energy level during cell differentiation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究による心筋分化過程の分子レベルでの解明は、心筋再生医療の発展に大きく貢献する。このような、細胞内のエネルギー状態をモニターするエピジェネティックなプロモーター制御の分子メカニズムの解明は、細胞内エネルギー代謝の変化に関わる遺伝子発現制御機構を理解するだけでなく、代謝経路が大きく変化する癌化のメカニズム解明のための極めて重要な手掛かりとなると考えられる。