Super-resolution imaging analysis of epigenetic states in the brain cells during aging

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15036
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kanazawa University
• Principal Investigator: Daisuke Ino 金沢大学, 医学系, 助教 (40721981)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: イメージング / ゲノム / 脳

Outline of Final Research Achievements

Owing to the extensive researches, it has been revealed that formation of “open chromatin”, a region where genomic DNA becomes loose and highly-accessible to the gene regulatory elements, is likely to be a key process to achieve the regulated gene expression. Thus, the technologies to study the 3D-organization of open chromatin have been developing. However, compared with the spatial information, the temporal information of open chromatin still remains limited, likely due to the lack of the suitable technology. In this work, we developed a new genetically-encoded fluorescent probe named ChrocodiLE, which enables us to visualize open chromatin dynamics in living cells. We generated ChrocodiLE-expressing animals (mice, nematodes, and flies). We believe that ChrocodiLE-expressing animals will be extremely helpful in studying the dynamics of open chromatin in a variety of cellular processes.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

近年次世代シーケンサーを用いたATAC-seqなどの方法により、オープンクロマチン領域の解析が活発に行われてきているが、生きた細胞内でのオープンクロマチン構造を解析できるツールは今まで存在しなかった。ChrocodiLEは本課題を解決するための世界初のツールである。特にChrocodiLEを発現する動物の作製に成功しているが、これらを疾患モデルと組み合わせることで、本研究分野のさらなる進展が期待できる。これらを活用することで、クロマチンの異常と病気の関連において、既存の手法では見えてこなかった現象が明らかになってくるであろう。