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2019 Fiscal Year Final Research Report

Establishment of germline-specific epigenome in mouse spermatogenesis

Research Project

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Project/Area Number 19K21196
Project/Area Number (Other) 18H06073 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0702:Biology at cellular to organismal levels, and related fields
Research InstitutionAzabu University

Principal Investigator

Maezawa So  麻布大学, 獣医学部, 講師 (90548174)

Project Period (FY) 2018-08-24 – 2020-03-31
Keywords生殖細胞 / エピジェネティクス / クロマチン / エンハンサー / 精子形成 / A-MYB
Outline of Final Research Achievements

Due to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. Much of this unique gene expression takes place when mitotic germ cells differentiate to enter into meiotic prophase. Here, analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super enhancers (SEs) drives bursts of germline gene expression after the mitosis-to-meiosis transition. At the mitosis-to-meiosis transition, mitotic SEs resolve while meiotic SEs are established. Meiotic SEs are associated with the activation of key germline genes, thereby defining the cellular identity of germ cells. This SE switching is regulated by the establishment of meiotic SEs via A-MYB (MYBL1), a key transcription factor for germline genes. Prior to entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia, serving to ensure the unidirectional differentiation of spermatogenesis.

Free Research Field

生殖科学

Academic Significance and Societal Importance of the Research Achievements

本研究では生殖細胞特異的な遺伝子発現を制御する活性化エンハンサーの動態を解明した。また、本研究によって新規に同定されたスーパーエンハンサーによって、精子形成期後期の分化進行に重要な遺伝子が制御されていることを見出した。さらに、A-MYB依存的なスーパーエンハンサーの形成機構を明らかにした。A-MYB依存的な生殖細胞特異的遺伝子発現は鳥類の精巣においても認められており、本研究で見出された分子機構は、進化的に保存された重要な精子形成遺伝子発現機構であると考えられる。本研究成果は、生体外での生殖細胞分化を制御する発生工学への応用や、ヒトの生殖医療の改善に役立つことが期待される。

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Published: 2021-02-19  

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