ヒストンH3ライシン9のメチル化により,HP1タンパク質の結合部位が形成されます
M Lachner1, D O'Carroll, S Rea
1Research Institute of Molecular Pathology, The Vienna Biocenter, Vienna, Austria.
Nature
|March 10, 2001
まとめ
哺乳類のメチルトランスフェラーゼ (Suv39h HMTases) は,ヒストンH3をメチル化することによってHP1タンパク質の結合部位を作成します. このSUV39H-HP1システムは,遺伝子の静止とヘテロクロマチン構造の維持に不可欠です.
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:
- ヒストンの改変は,遺伝子のアクセシビリティと発現を調節する.
- 遺伝子発現を制限することは,細胞および発達プロセスにとって不可欠です.
- ヘテロクロマチンの形成には,遺伝子サイレンシングと超核染色体クロマチンの構造が含まれます.
研究 の 目的:
- ヘテロクロマチンの形成における哺乳類メチルトランスファーゼ (Suv39h HMTases) の役割を調査する.
- ヒストンのメチル化とHP1タンパク質結合を結びつける分子メカニズムを解明する.
- SUV39H-HP1システムがヘテロクロマティックサブドメインにどのように貢献するのかを理解するために.
主な方法:
- メチル化ヒストンH3ペプチドとHP1タンパク質を用いたインビトロ結合試験.
- Suv39hのダブルニールマウスの線維芽細胞におけるヘテロクロマチンとHP1タンパク質の関連性の分析.
- 触媒的に活性なSWUV39H1 HMTaseの再導入によりHP1関連性の回復.
主要な成果:
- Suv39h HMTasesは,ライシン9上のヒストンH3をメチル化し,HP1タンパク質の結合部位を生成する.
- HP1タンパク質のクロモドメインは,ヒストンH3.3上のメチル化リシン9エピトープを特異的に認識する.
- ヘテロクロマチンとHP1タンパク質の関連性は,Suv39h HMTaseの活性 in vivo に依存しています.
- SWUV39H1の再導入により,Suv39h欠乏細胞におけるHP1ヘテロクロマチン関連が回復する.
結論:
- SUV39H-HP1メチル化システムは,HP1がメチル化ヒストンH3.3に結合するための分子メカニズムを提供します.
- このシステムは,ネイティブクロマチンのヘテロクロマティックサブドメインの伝播に不可欠です.
- Suv39h HMTasesによるヒストンH3ライシン9メチル化は,ヘテロクロマチンの確立と維持における重要なイベントです.
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