Comprehensive identification and functional elucidation of regulators of histone modifications that regulate germ cell fate

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17594
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology); Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: Mochizuki Kentaro 東北大学, 医学系研究科, 大学院非常勤講師 (20633499)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 始原生殖細胞 / ヒストン修飾

Outline of Final Research Achievements

An organism is composed of germ cells and somatic cells. In mammals, including humans, germ cells only ensure the succession of generations through fertilization, after forming a sperm or egg. Germ cell abnormalities can cause infertility and a variety of diseases that offspring carry. In this research, we succeeded in comprehensively identifying histone modification enzymes that play a role in the emergence of primordial germ cells from among about 200 enzymes that are responsible for acetylation, methylation, and phosphorylation of histones, which are nuclear proteins that are important for gene switching on and off. In particular, we demonstrated in detail that a demethylase represses the expression of a set of genes responsible for differentiation into somatic cells and that a methyltransferase contributes to the emergence of primordial germ cells by guaranteeing signaling pathways.

Free Research Field

発生生物学、エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

本研究から、始原生殖細胞の出現を促進するヒストン修飾、ならびに抑制するヒストン修飾がフルセットで明らかになり、分子ネットワークの全体像に切り込む突破口が見えてきた。また、始原生殖細胞の出現は生殖細胞の発生分化の初発段階に位置することから、そこで機能するヒストン修飾は、後の段階のヒストン修飾のパターン確立に関わり、精子／卵子形成、受精、次世代個体の発生にも大きな役割を担う可能性が高い。本研究成果は、そのようなヒストン修飾を明らかにしたことから、生殖細胞の発生分化の理解に大きく貢献できる。