Elucidating transcriptional dynamics control via the formation of nuclear microenvironments

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03154
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Fukaya Takashi 東京大学, 定量生命科学研究所, 准教授 (00786163)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ショウジョウバエ / エンハンサー / 転写バースト / 転写因子

Outline of Final Research Achievements

We have successfully developed a super-resolution live-imaging technique to simultaneously visualize the nuclear dynamics of transcription factors and gene expression. Through detailed analysis, we have elucidated that enhancers control the spatiotemporal dynamics of gene expression via dynamic changes in the local concentration of transcription factors. Moreover, we have discovered a novel mechanism of gene expression regulation, in which two distant genes located far apart on the genome are simultaneously controlled by sharing a cluster of transcription factors. Using genome-editing analysis in Drosophila, we experimentally demonstrated that aberrant accumulation of the local concentration of transcription factors disrupts the spatiotemporal pattern of gene expression, leading to severe developmental defects.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、生物の持つゲノム情報がどのように正確に読み出されているのか、というセントラルドグマにおける基本原理の謎の解明につながる画期的成果である。また、転写因子の異常凝集は癌をはじめとするさまざまな疾患との関連が報告されていることから、本研究によって得られた知見はは多様な疾患メカニズムの解明や新規治療法の開発へ向けた基盤的知見となるものと期待される。