マウスの卵細胞における広範囲ヒストンH3K4me3ドメインは,母体からシゴティックへの移行を調節する
John Arne Dahl1, Inkyung Jung2, Håvard Aanes1
1Department of Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027 Oslo, Norway.
Nature
|September 15, 2016
まとめ
マザー・ツー・ジゴティック・トランジション (MZT) は,ダイナミックなヒストンの変化を伴う. 新しいマイクロスケールChIP-seqは,卵細胞内の広範囲のH3K4me3ドメインが,生殖細胞のゲノム活性化と早期胚発育に不可欠であることを明らかにしています.
科学分野:
- 発達生物学
- エピジェネティクス
- ゲノミクス
背景:
- 胎児発達の開始には,母から胎児発育への移行 (MZT) が重要であるが,まだ十分に理解されていない.
- MZT中にクロマチンの状態を直接測定することは,限られた細胞数のために困難です.
- ヒストンの改変はMZTに関与しているが,その正確な役割と動態は不明である.
研究 の 目的:
- 初期のマウス胚におけるヒストンの改変をプロファイリングするためのマイクロスケールクロマチンの免疫降水とシーケンシング (μChIP-seq) 方法を開発し,適用する.
- MZT中のヒストンH3リジンメチル化 (H3K4me3) とアセチル化 (H3K27ac) の全ゲノム分布と動態を調査する.
- 特定ヒストンの改変がジゴトのゲノム活性化と初期胚の発達における役割を明らかにする.
主な方法:
- 微量クロマチンの免疫降水と配列化 (μChIP-seq) 測定法を開発し,少量の細胞から分析を可能にします.
- マウスの卵細胞 (未成熟およびメタフェーズII) および初期胚 (2細胞および8細胞段階) の全ゲノムH3K4me3およびH3K27acのプロファイリング.
- MZT中のヒストンの改変,DNAメチル化,遺伝子発現の関係に関する分析.
主要な成果:
- 約22%の卵細胞ゲノムは,DNAメチル化と逆相関する広範囲のH3K4me3ドメインを示しています.
- H3K4me3ドメインは,広範囲のパターンから2細胞胚の転写開始部位特異的局所化へと移行し,ジゴティックゲノム活性化に一致する.
- KDM5AとKDM5Bによる広範なH3K4me3ドメインの活性除去は,正常なシゴティックゲノム活性化およびその後の発達に不可欠です.
結論:
- 卵細胞内の広範囲のH3K4me3ドメインは,母体から卵巣への移行を調節する上で重要な役割を果たします.
- H3K4me3の動的調節,特にKDM5A/Bによる除去は,成功するジゴティックゲノム活性化と早期マウス胚の発達に不可欠である.
- 開発されたμChIP-seqメソッドは,発達中の限られた細胞集団における表遺伝子動態を研究するための強力なツールを提供します.
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