Molecular mechanism of DNA methylation-mediated epigenome memory and its functional implications

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05331
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kyushu University (2017-2018); Tokyo Medical and Dental University (2016)
• Principal Investigator: Ogawa Yoshihiro 九州大学, 医学研究院, 教授 (70291424)
• Research Collaborator: Hashimoto Koshi ; Yuan Xunmei ; Tsujimoto Kazutaka ; Kawahori Kenichi ; Hanzawa Nozomi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: エピゲノム記憶 / DNAメチル化 / FGF21 / PPARα

Outline of Final Research Achievements

Fibroblast growth factor 21 (FGF21; Ffg21) is a major PPARα target gene that occurs abundantly in the liver. We have found that DNA demethylation of Fgf21 can be modulated and/or enhanced by pharmacologic activation of PPARα during the suckling period. Importantly, DNA methylation status of Fgf21, once established in early life, is relatively stable and remains into adulthood as an epigenetic memory. With increased DNA demethylation, hepatic induction of Fgf21 has been exaggerated upon PPARα activation, which may account in part for the attenuation of diet-induced obesity in adulthood. This study represents the first demonstration that DNA methylation status of a particular gene, once established in early life, contributes to the metabolic phenotypes in later life.

Free Research Field

内科学、内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

早期ライフステージにおけるエピゲノム記憶の担い手としてDNAメチル化の生理的・病態生理的意義が示唆された。本研究の学術的意義としては、特定の遺伝子のDNAメチル化状態が早期ライフステージの記憶・維持を担うことにより将来の疾患発症に関与することが初めて証明された。一方、社会的意義としては、人工乳や機能性食品によるエピゲノム制御による胎児期や新生児期の栄養環境に対する介入により、成人期に発症する生活習慣病の先制医療の実現が期待される。