Characterizing the roles of oocyte-specific factors in inhibiting unique features of the sperm epigenome

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15125
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Osaka University
• Principal Investigator: SHIRANE Kenjiro 大阪大学, 大学院医学系研究科, 講師 (50855004)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 卵母細胞 / エピゲノム性差 / DNAメチル化

Outline of Final Research Achievements

This study aimed to elucidate the mechanism that prevents sperm-type epigenome in oocytes. To this end, we generated embryonic stem cells depleted of a candidate factor for this mechanism and reconstructed ovaries using these cells. Genome-wide DNA methylation analysis of mutant oocytes revealed that this factor is not involved in preventing sperm-type DNA methylation patterns in oocytes. Intriguingly, however, this factor is localized to the cytoplasm rather than the nucleus. This observation is particularly interesting, as typical epigenetic modifiers are active in the nucleus, suggesting a novel role for this factor in the cytoplasm of oocytes. In addition, we identified key transcription factors that activate this cytoplasmic factor in oocytes. In summary, we revealed transcriptional regulation of this factor and the role on the epigenetic regulation in oocytes. However, the role in the cytoplasm of oocytes warrants further investigation.

Free Research Field

エピゲノム

Academic Significance and Societal Importance of the Research Achievements

卵子と精子の持つ異なるエピゲノムパターンは個体の発生に必須であり、その分子基盤の解明は生物学的・医学的に大きな意義を持つ。本研究では、卵母細胞において精子型エピゲノム獲得を抑制する候補因子の一つに着目した。体外で卵母細胞の発生を再構築する実験系から、その発現制御機構の一端やその因子が直接的に卵母細胞のDNAメチル化パターンの形成に寄与しないことを明らかにした。加えて、この因子が細胞質に局在するという予想外の結果を得た。これは、卵母細胞が精子型のエピゲノム制御因子の機能を変化させる新たな機構の一つを示唆する。この因子の更なる解析は配偶子間の異なるゲノム機能の使い分けの理解につながると期待できる。