ヒストンH3.3のリン酸化は刺激誘発の転写を強化する

Anja Armache^1,2, Shuang Yang³, Alexia Martínez de Paz¹

¹Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

Nature

|July 24, 2020

まとめ

Ser31でのヒストン変異体H3.3リン酸化 (H3.3S31ph) は,マクロファージにおける急速な遺伝子誘導を可能にします. このマークは転写因子を誘発し,抑制剤を放出し,より迅速な遺伝子活性化を促します.

科学分野:

分子生物学
エピジェネティクス
細胞生物学

背景:

複雑な生物における遺伝子誘導はクロマチンの調節に依存している.
ヒストン変種H3. 3は動的に調節されたクロマチンで濃縮されています.
誘発された遺伝子の高速で高レベルの転写を可能にするメカニズムは不明である.

研究の目的:

急速な遺伝子誘導におけるヒストン変異体H3.3の役割を調査する.
転写を容易にするH3.3の特定の特徴を特定する.
刺激反応性遺伝子調節の基礎にある分子メカニズムを解明する.

主な方法:

マウスのマクロファージにおけるヒストンの変化の分析.
相互作用するタンパク質を特定するための質量スペクトロメトリー
ヒストン変異の局所化を評価するクロマチンの免疫流出.

主要な成果:

セルリン31 (H3.3S31ph) でのH3.3のリン酸化は,迅速に誘導された遺伝子で発生する.
H3.3S31phはヒストンメチルトランスファーゼSETD2を選択的に誘導する.
H3.3S31phは,延長コアプレッサーZMYND11のエジェクションを容易にする.

結論:

H3.3S31phは刺激反応性遺伝子の鍵となるマーカーです.
このリン酸化は,転写装置の特権的なアクセスを提供します.
H3. 3 リン酸化を含む専用メカニズムは,急速な転写を調節する.

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