Elucidation of the Integrated Epigenomic Control Mechanisms by Metabolic Environment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03729
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Gunma University
• Principal Investigator: Inagaki Takeshi 群馬大学, 生体調節研究所, 教授 (10507825)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エピゲノム

Outline of Final Research Achievements

The epigenome, which senses metabolic environment, is involved in the control of cellular differentiation. Iron is essential for the activity of histone demethylase and DNA demethylase. In the process of adipocyte differentiation, we discovered that stored iron in cells is supplied by ferritinophagy. We also found that the iron chaperone PCBP migrates to the nucleus, and this plays a crucial role in adipocyte differentiation. Furthermore, after the induction of adipocyte differentiation, the activity of the histone demethylase JMJD1A and the DNA demethylase TET2 is regulated in an iron-dependent manner, leading to the rewriting of the epigenome. As a result, the expression of genes related to adipocyte differentiation is induced, and we elucidated the mechanism of adipocyte differentiation through this series of events.

Free Research Field

代謝エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

肥満症や糖尿病の発症機序を理解するうえで、脂肪細胞の分化制御機構を解明することは重要である。今回、脂肪細胞分化にかかわるDNAメチル化やヒストンメチル化修飾といったエピゲノムの書き換えにおいて、鉄が重要な役割を果たすことを見出した。この新たな脂肪細胞分化の制御機構の提示は、肥満症や糖尿病の新しい治療戦略に寄与する可能性がある。