Establishment of an imaging system for environment-induced epigenome alterations

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07628
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Hoshi University (2022); National Cancer Center Japan (2020-2021)
• Principal Investigator: Hattori Naoko 星薬科大学, 先端生命科学研究所, 特任准教授 (30611090)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エピジェネティクス / DNAメチル化 / 環境要因 / がん

Outline of Final Research Achievements

In this study, my aim was to develop an imaging system for detecting epigenome alterations caused by exposure of environmental factors. Firstly, I constructed a vector containing tetracycline-responsive element and EF1α promoter upstream of the mCherry gene, along with a T2A sequence and a puromycin-resistant gene. Additionally, I employed a knock-in system using the CRISPR/Cas9 system to insert the gene downstream of the endogenous promoter. To confirm the effectiveness of the imaging system, I developed a system to induce gene-specific DNA methylation using the CRISPR-dCas9-Dnmt3a system. Moreover, to identify promoters that are sensitive to aberrant DNA methylation triggered by chronic inflammation, I conducted a genome-wide DNA methylation analysis on colonic epithelial cells from mice administered with dextran sulfate.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

環境要因への曝露は発がんの関連要因もしくは原因であるが、その分子機構は不明な点が多い。本システムによって、エピゲノム異常からの発がんの分子機構が解明されるだけでなく、エピゲノム異常誘発の抑制・解除によるがん予防の効果をモニターすることが可能となる。将来的には、新たながん予防法の開発や新規のエピゲノム異常誘発要因の同定に繋がる。