Study on flavin-dependent epigenome that links nutritional environment to phenotype

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04108
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kumamoto University
• Principal Investigator: Hino Shinjiro 熊本大学, 発生医学研究所, 准教授 (00448523)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: リボフラビン / エピゲノム / LSD1 / 栄養素代謝 / ミトコンドリア

Outline of Final Research Achievements

Riboflavin (Rf) is an essential micronutrient. However, its long-term effects on tissue development and homeostasis remain unknown. In this project, we explored how Rf contributes to cellular functions and tissue homeostasis through the modulation of epigenetic and transcriptional factors such as histone demethylases LSD1 and LSD2. Within the duration of this project, we revealed the contribution of Rf metabolism in tissue homeostasis, the regulation of metabolic phenotypes and environmental responses by LSD1, and the mechanisms of mitochondria-to-nucleus signaling. Overall, we succeeded in elucidating the intimate relationship between nutrient metabolism and epigenetic gene regulation.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

本研究により、Rf代謝や様々な環境ストレスが細胞内代謝やシグナル伝達を介して転写・エピゲノム制御に作用する仕組みやその環境適応や組織恒常性における役割を明らかにすることができた。また、Rf依存的活性を持つLSD1が筋肉の加齢性変化に関わる可能性を報告した。これらの成果は、Rf摂取の多寡が健康寿命に影響を及ぼす可能性を示唆しており、今後の応用展開が期待できる。また、本研究で構築した研究アプローチは、後続の栄養エピジェネティクス研究に幅広く活用できるものである。