Challenges in Artificial Editing of Epigenomic Memory Underlying Lifestyle-related Diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22633
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• 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): 2019-06-28 – 2022-03-31
• Keywords: エピゲノム / SunTag法 / ヒストンメチル化修飾

Outline of Final Research Achievements

Histone methylation is involved in the regulation of adipocyte differentiation. Therefore, artificial regulation of histone methylation is expected to affect gene expression related to adipocyte differentiation. In this study, we attempted to recruit the histone methyltransferase SETDB1 to a target genomic region using the SunTag method. We found that histone H3K9 methylation levels were increased in the region encoding Cebpa, a master regulator of adipocyte differentiation, and that Cebpa expression was suppressed. We also found that this change is dependent on the enzymatic activity of SETDB1.

Free Research Field

代謝エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

飽食の時代を生きる私たちにとって、肥満症の制御は重要な課題である。脂肪を構成する脂肪細胞の分化の制御にはヒストンメチル化修飾というエピゲノム機構が関与する。本研究ではSunTag法を用いてヒストンメチル化酵素であるSETDB1を標的遺伝子領域に動員することで、脂肪細胞分化関連遺伝子であるCebpaの発現を制御することに挑戦し、遺伝子発現が抑制されることを見出した。この成果は、人工的に脂肪細胞のヒストンメチル化修飾を書き換えるための基盤技術を立ち上げたものであり、将来的に肥満症治療の新規戦略などへの応用が期待される。