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 |
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
Keywords | エピゲノム / エピジェネティクス / 脂肪細胞分化 |
Outline of Research at the Start |
本研究は、肥満や糖尿病と関係の深い脂肪細胞をモデルとして利用して実施する研究である。細胞内に存在する代謝物が、細胞内エネルギー環境を感知するセンサーとして働くという仮説に基づき、「代謝物によってエピゲノムが書き換えられることで、転写から翻訳までのセントラルドグマを一元的に制御する機構」の存在を予想して解明することを目指すものである。
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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.
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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。
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