哺乳類初期発生におけるDNAメチルームとトランスクリプトームの動態を解明(Fan Zhou’s group uncovers DNA methylome-transcriptome dynamics in early mammalian development)

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2025-08-27 清華大学

2025年6月3日、清華大学生命科学学院の范舟(Fan Zhou)教授の研究グループが、Cell Reports誌に「Dissecting pre- to post-implantation transition of DNA methylome-transcriptome dynamics in early mammalian development」という研究論文を発表しました。同研究では、哺乳類の着床前後の発生過程におけるDNAメチル化(DNAme)とトランスクリプトーム(RNA発現)のネットワーク動態を、高解像度・技術中立的かつ種を跨いだ視点で包括的に解析しました。DNAメチル化は、転写調節、ゲノム刷り込み、X染色体の不活化、細胞運命の決定や状態遷移などに重要な役割を果たしますが、胚発生の初期段階でこれらがどのように再プログラムされるかを統合的に解析したシステム的研究はこれまで存在しませんでした。本研究は、着床周辺における系統ごとの段階的なゲノム沈静化(gene silencing)が、新規のDNAメチル化(de novo DNAme)を伴って進行するプロセスを明らかにしました。

哺乳類初期発生におけるDNAメチルームとトランスクリプトームの動態を解明(Fan Zhou’s group uncovers DNA methylome-transcriptome dynamics in early mammalian development)Figure 1. Emergence of lineage-specific DNAme in early mammalian development

<関連情報>

哺乳類初期発生におけるDNAメチルーム-トランスクリプトーム動態の着床前~着床後移行過程の解明 Dissecting pre- to post-implantation transition of DNA methylome-transcriptome dynamics in early mammalian development

Qingyuan Zhu ∙ Ying Liu ∙ Xin Hao ∙ … ∙ Changqing Zheng ∙ Xianwen Ren ∙ Fan Zhou
Cell Reports  Published:June 3, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.115790

Highlights

  • Species-conserved lineage-specific DNA methylation remodeling occurs during PPT
  • Visceral endoderm subtypes show segregated methylation dynamics
  • DNA methylation difference of parental transposons reveals asynchronous erasure
  • Identified promoters exhibit non-canonical DNA methylation-transcription coupling

Summary

Pre- to post-implantation transition is an essential step for early mammalian development. The epigenome dynamics such as DNA methylome and transcriptome of embryos have been analyzed, while the coordination between these two molecular layers controlling lineage fate remained elusive. Here, with a multidimensional profiling of peri-implantation embryos, we present the emerging lineage-specific DNA methylation (DNAme) patterns across species. The maternal and paternal DNA methylation levels exhibit differential dynamics in transposon elements. Genes with lineage-specific unmethylated promoters early in development retain this state and are expressed later, suggesting a role in lineage fate determination. By measuring both molecular dimensions simultaneously in individual developing cells, we identified a group of gene promoters with positive correlation between DNAme and RNAex along epiblast development. Functional validation suggested DNAme at these promoters contributes to non-canonical DNAme-RNAex dynamics, potentially via complex TF-mediated or epigenetic regulation. This study provides clues for understanding molecular regulation of peri-implantation embryogenesis.

細胞遺伝子工学
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