Development and applications of next-generation epigenomics technologies

2021 Fiscal Year Final Research Report

• Project Area: Transomic Analysis of Metabolic Adaptation
• Project/Area Number: 17H06305
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: Ito Takashi 九州大学, 医学研究院, 教授 (90201326)
• Co-Investigator(Kenkyū-buntansha): 梅山 大地 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (30706370) ; 荒木 啓充 九州大学, 経済学研究院, 助教 (60572823)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: DNAメチル化 / ゲノムフットプリンティング / セルフリーDNA / DNAメチル化酵素

Outline of Final Research Achievements

In this project, we aimed to develop highly-sensitive and/or multiplexed epigenome sequencing methods, which should be critical to accelerate trans-omic analyses. First, we developed a highly efficient method for single-stranded DNA ligation termed TACS ligation and introduced it to further improve the performance of PBAT, the most sensitive and reliable methylome sequencing method of our own. Second, we developed DMS-seq for in vivo genome-wide mapping of protein-DNA interactions and nucleosome centers, thus adding a unique method to the toolbox for epigenomics. Third, we applied TACS ligation to cell-free DNA analysis and revealed a novel class of short single-stranded DNA enriched with noncanonical DNA structure, or antisense of G-quadruplex structure. Fourth, we identified a novel DNA methyltransferase, which should lay a basis for a multiplexed epigenomics method to encode histone modification information to methylation of neighborhood DNA.

Free Research Field

ゲノム科学

Academic Significance and Societal Importance of the Research Achievements

全ゲノムバイサルファイトシーケンシングにおいて有数の実績を残してきたPBAT法が新技術TACSライゲーションの開発によって更に高度化されて支援に活用されたことによって、メチローム解析を含む多彩な研究が数多く促進された。更に新規ゲノムフットプリント法の開発により、エピゲノム解析手法のレパートリーが拡がった。また長らく見落とされてきた新規クラスの発見によって、血中セルフリーDNAの全貌を明らかにした。