Understanding the mechanism why cardiac myocytes resist Myc-induced proliferation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08854
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Kyohei Oyama 旭川医科大学, 医学部, 講師 (00818479)
• Co-Investigator(Kenkyū-buntansha): 紙谷 寛之 旭川医科大学, 医学部, 教授 (30436836)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Trim28 / エピジェネティクス / 転写調節 / 脂質代謝 / H3K9メチル化

Outline of Final Research Achievements

Trim28 is a chromatin regulatory factor involved in various processes, including development, metabolism, and gene expression, through deposition of histone H3K9 methylation. Previously, we have discovered that H3K9me3 is associated with the inhibition of cardiac myocyte proliferation. This study investigated if Trim28 was involved in the regulation of cardiac myocyte proliferation using cardiac specific Trim28 knockout mice. Contrary to the hypothesis, Trim28 had minimal impact on cardiac myocyte proliferation and H3K9 methylation status. However, detailed analysis revealed that Trim28 plays a promotive role in the expression of fatty acid metabolism genes in cardiac myocytes.

Free Research Field

心筋細胞のエピジェネティック制御

Academic Significance and Societal Importance of the Research Achievements

心筋細胞は高度の分化した細胞で、分裂や代謝の制御が特殊化している。正常な心臓は脂肪酸を主要なエネルギー源と利用しているが、病態下では脂肪酸代謝の異常が生じ心不全の進行に関わることが知られている。本研究では、これまで知られていなかった脂肪酸代謝の遺伝子発現を制御するメカニズムの一端を明らかにした。また、遺伝子発現において抑制的な機能を持つと考えられていたクロマチン制御因子が、促進的な作用を示す新たな知見を得た。