ドロソフィラ・ポリコンブ群の抑制剤複合体のヒストンメチルトランスフェラーゼ活性
Jürg Müller1, Craig M Hart, Nicole J Francis
1EMBL, Gene Expression Programme, Meyerhofstr. 1, 69117 Heidelberg, Germany. mueller@embl-heidelberg.de
Cell
|November 1, 2002
まとめ
ポリコンブ群 (PcG) タンパク質は遺伝子発現を調節する. この研究では,Enhancer of Zeste [E(Z]タンパク質をヒストンメチルトランスフェラーゼとして識別し,開発中のPcG媒介の転写抑制に不可欠です.
科学分野:
- 発達生物学 発達生物学について
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
背景:
- ポリコンブ群 (PcG) タンパク質は,発達中の転写抑制を維持するために不可欠です.
- PcGタンパク質は抑圧的な染色体状態を確立するが,鍵となる複合体の正確な組成と生化学的機能は不明である.
- エクストラ・セックス・コンブ (ESC) とエンハンスター・オブ・ゼステ (Enhancer of Zeste, E(Z) タンパク質は,重要なPCG複合体のコアコンポーネントである.
研究 の 目的:
- ESC-E(Z) ポリコンブ群複合体の構成と生化学的活性を解明する.
- E(Z) タンパク質が酵素活性を持っているかどうかを判断するために,特にヒストンメチルトランスフェラーゼ機能.
- PcG媒介による遺伝子サイレンシングにおけるヒストンメチレーションの役割を調査する.
主な方法:
- ドロソフィラの胚からESC-E(Z) 複合体の浄化.
- 浄化されたサブユニットを使用して再結合複合体の再構成.
- 復元された複合体を用いた in vitro メチルトランスフェラーゼアッセイ.
- 変異したE (((Z)) タンパク質の活性とインビヴォの遺伝子抑制の分析.
主要な成果:
- 精製されたESC-E(Z) 複合体は,ESC,E(Z),NURF-55,SU(Z) の4つのサブユニットで構成されています.
- 再構成された複合体はメチルトランスフェラーゼ活性を示し,特にヒストンH3のライシン-27をメチル化する.
- E(Z) SETドメインの変異により, in vitroではメチルトランスフェラーゼの活性が廃止されます.
- E(Z) SETドメインの機能の障害は,HOX遺伝子の抑制が vivo で損なわれることにつながります.
結論:
- Enhancer of Zeste [E(Z]タンパク質は,酵素メチルトランスファーゼ活性を持つポリコンブ群タンパク質として識別されています.
- ヒストンH3リジン-27メチレーションは,ポリコンブ媒介による転写サイレンシングの重要なメカニズムとして関与しています.
- この研究は,PcG複合体の組成と,開発の表遺伝的調節を結びつける生化学的証拠を提供します.
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