Omics approaches towards the elucidation of the molecular network regulating the developmental capacity of the mammalian oocyte

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H05214
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: SASAKI Hiroyuki 九州大学, 生体防御医学研究所, 特別主幹教授 (30183825)
• Co-Investigator(Kenkyū-buntansha): 丸山 修 九州大学, 芸術工学研究院, 准教授 (20282519)
• Project Period (FY): 2018-04-23 – 2023-03-31
• Keywords: 卵子 / オミックス / ゲノム編集 / 機械学習 / 発生 / エピジェネティクス

Outline of Final Research Achievements

By applying genome editing and small-scale omics approaches, we have revealed the molecular network regulating histone modifications and DNA methylation in mouse oocytes, which are essential for mammalian development. We discovered that several histone modifications impact the efficiency and distribution of DNA methylation and identified the proteins and their domains that mediate the epigenetic crosstalk. Further, we found that, while DNA methylation established in oocytes regulates the expression of the maternally imprinted genes almost exclusively in embryos, histone modifications and their responsive factors have a wider effect and regulate various cellular function including chromosome segregation. Finally, we developed a machine-learning-based model that predicts the heritability of DNA methylation to the next generation based on DNA sequence. The findings provide a basis for the study of infertility, various diseases, and improvement of assisted reproductive technologies.

Free Research Field

分子生物学、遺伝学、発生学、エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

我々が明らかにしたマウス卵子におけるヒストン修飾とDNAメチル化の分子ネットワークは、不妊・流産・先天異常の原因解明、及び生殖補助医療技術の改善に資すると考えられ、ヒト人工多能性幹細胞から誘導された卵細胞のエピゲノムデータは、この細胞の学術的・臨床的応用に向けて貴重な情報リソースである。また、我々が開発した数理モデルは、子宮内環境や種々の環境ストレスにより生じたエピゲノム異常の次世代への伝達の予測に役立つほか、その機構の解明に貢献すると期待される。