Jarid2/Jumonjiは,PRC2の酵素活性と多能細胞の標的遺伝子占有量の制御を調整しています
Jamy C Peng1, Anton Valouev, Tomek Swigut
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|January 13, 2010
まとめ
Jarid2は,胚性幹細胞における新しいポリコンブ抑制複合体2 (PRC2) サブユニットである. それは,発達と細胞の分化のための遺伝子調節を微調整します.
科学分野:
- エピジェネティクスと遺伝子調節
- 発達生物学 発達生物学について
- 幹細胞生物学 幹細胞生物学
背景:
- ポリコンブ抑制複合体2 (PRC2) は,胚性幹細胞 (ES) の発達遺伝子の調節に不可欠である.
- ES細胞と早期発達におけるPRC2の正確な役割を理解することは,細胞運命を制御するために不可欠です.
- Jumonji C (JmjC) ドメインのタンパク質であるJarid2は,多能細胞で濃縮されていることが知られている.
研究 の 目的:
- ES細胞におけるPRC2のサブユニットとしてのJarid2の役割を調査する.
- Jarid2がPRC2のゲノム結合と酵素活性にどのように影響するか解明する.
- 開発初期におけるJarid2とPRC2の相互作用による機能的影響を決定する.
主な方法:
- ES細胞におけるJarid2,Ezh2,Suz12の全ゲノムChIP-seq分析. ES細胞におけるJarid2,Ezh2,Suz12の全ゲノムChIP-seq分析. ES細胞におけるJarid2,Ezh2,Suz12の全ゲノムChIP-seq分析. ES細胞におけるJarid2,Ezh2,Suz12の全ゲノムChIP-seq分析.
- PRC2ヒストンメチルトランスフェラーゼの活性を評価するための生化学分析.
- Jarid2ノックダウンによるXenopus laevis胚を用いた機能研究.
主要な成果:
- Jarid2は,ES細胞におけるPRC2のサブユニットとして識別される.
- Jarid2とPRC2は,同じゲノム領域で共局所する.
- Jarid2は,PRC2の標的遺伝子へのリクルートを強化するが,メチルトランスフェラーゼの活性を抑制し,分子リオスタットとして作用する.
- Xenopusの胚におけるJarid2のノックダウンは, gastrulation遺伝子の誘導と分化を妨害する.
結論:
- Jarid2はPRC2の重要な成分であり,多能細胞におけるその機能を調節する.
- この相互作用は,発達性遺伝子の正確な表遺伝的調節に不可欠です.
- この発見は,早期の細胞-フェット移行時にヒストンのメチル化を制御するための新しいメカニズムを明らかにしています.
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