Cul4 E3ユビキチンリガゼは,核細胞組立中にヒストンの引き渡しを調節する
Junhong Han1, Hui Zhang, Honglian Zhang
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Cell
|November 12, 2013
まとめ
ヒストンチャペロンAsf1は,新たに合成されたH3-H4.4を結合する. 保存されたE3リガゼは,アセチル化H3をユビキチル化のために標的にし,H3-H4の転送と核細胞組成を促進します. これはヒストンアセチル化とユビキチル化との交差を明らかにする.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- クロマチンの生物学
背景:
- 核細胞組成は,DNA複製と転写後のゲノム安定性および表遺伝的継承に不可欠である.
- Asf1を含むヒストンチャペロンは,新たに合成されたヒストンH3-H4.4を管理する.
- H3-H4をAsf1から他のシャペロンに転送するメカニズムは,Asf1の高い親和性のために不明のままです.
研究 の 目的:
- Asf1チャペロン複合体からのH3-H4の移転を調節するメカニズムを調査する.
- 核細胞組立のためのH3-H4の放出を媒介する要因を特定する.
- この過程におけるヒストンアセチル化とユビキチル化の相互作用を探求する.
主な方法:
- Rtt101 (((Mms1) E3ユビキチンリガゼを研究するために酵母モデルを使用しました.
- ヒストンH3の結合と普遍化を研究し,特にライシン56でアセチル化した.
- Rtt101とH3.3の遺伝子不活性化とサイト指向型変異を生成した.
- 核細胞組成効率とAsf1-H3の相互作用を調べました.
- Cul4A (((DDB1) 枯渇を用いたヒト細胞での確認された発見.
主要な成果:
- 酵母Rtt101 (((Mms1) E3ユビキチンリガゼは,ライシン56でアセチル化された新たに合成されたヒストンH3を特異的に結合し,ユビキチラートする.
- Rtt101の無活性化や,H3のユビキティレーション部位の変異は,核細胞組成を阻害する.
- これらの遺伝的変異はまた,Asf1とH3の相互作用を強化します.
- ヌクレオソーム組立の類似の欠陥と変化したチャペロン相互作用は,Cul4A (((DDB1) が欠けているヒト細胞でも観察されました.
結論:
- 保存されたE3リガゼ (Rtt101 (((Mms1) /Cul4A (((DDB1)) は,Asf1チャペロン複合体からのH3-H4の移転を調節する.
- 特にK56でのヒストンH3の普遍化は,この移転を促進する重要なステップです.
- ヒストンアセチル化とユビキチル化の交差が,核細胞組成と表遺伝子維持の調節において示されている.
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