Analysis of gene expression mechanism regulated by nutrition signal using in vivo imaging

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05060
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: University of Tsukuba
• Principal Investigator: Takeuchi Yoshinori 筑波大学, 医学医療系, 助教 (70508093)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 栄養代謝 / 脂質代謝 / 転写

Outline of Final Research Achievements

In order to analyze the detailed mechanism of SREBP-1c gene regulation in vivo, which is important for the regulation of lipid synthesis in liver, I developed the cis sequence identification method using adenovirus reporter vector and in vivo imaging system (in vivo Ad-Luc). Simultaneously, I also applied the trans factor identification method through Transcription Factor Expression plasmid Library "TFEL" (TFEL scan) and found that KLF15 is important for the regulation of SREBP-1c expression in liver. It is known that KLF15 expression is upregulated during fasting, however, its regulatory mechanism has not yet been revealed. Therefore I investigated the regulatory mechanism of hepatic KLF15 gene expression by in vivo Ad-luc method and TFEL, and found new genomic region that important for KLF15 gene regulation during fasting and an important transcription factors binding to the region.

Free Research Field

栄養代謝

Academic Significance and Societal Importance of the Research Achievements

本研究において、研究代表者が独自に開発した、生体での遺伝子発現調節機構の網羅的解析手法にて、肝臓において栄養状態により発現が変動するKLF15遺伝子の新たな調節機構を世界で初めて明らかにすることに成功した。現在、その研究結果をまとめ国際的な学術雑誌に論文として投稿する準備を進めている。肝臓でのKLF15は糖代謝や脂質代謝異常に関する治療のターゲットとなりうることが示されているため、本研究によって見出されたKLF15遺伝子の新たな発現調節機構を軸として、画期的な生活習慣病の治療法が確立されることが期待できる。