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誘導可能な遺伝子発現の制御は,信号依存の転写延長によって行われます
Diana C Hargreaves1, Tiffany Horng, Ruslan Medzhitov
1Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cell
|July 15, 2009
まとめ
主要応答遺伝子 (PRG) は,迅速な遺伝子発現のために,事前に組み立てられた転写機構を有しています. 彼らの誘導は, Brd4媒介のP-TEFb採用によって促進される,信号依存の延長とmRNA処理に依存しています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- エピジェネティクス エピジェネティクス
背景:
- 誘導性トランスクリプションプログラムには,異なる発現運動を持つ主および二次応答遺伝子 (PRGおよびSRG) が含まれる.
- PRGとSRGは,遺伝子活性化中にタンパク質合成とクロマチンの改造に関する要件によって異なります.
研究 の 目的:
- PRGとSRGの基礎状態の特徴を調査する.
- PRGの急速な誘導を制御する規制メカニズムを明らかにする.
- PRGの活性化に関与する重要なタンパク質と改変を特定する.
主な方法:
- 基礎状態のPRGプロモーターにおけるプリアセンブリされたRNAポリメラーゼII (Pol II) とヒストンの改変の分析.
- PRG誘導中の転写延長とmRNA処理の調査.
- PRGの活性化におけるP-TEFbとBrd4の役割の検討.
- PRGプロモーターにおけるヒストンアセチル化 (H4K5/8/12Ac) の検出.
主要な成果:
- 多くのPRGは,SRGとは異なり,プリアセンブリされたPol IIと陽性ヒストンの改変を基本的にはプロモーターで表しています.
- PRGのベースポルIIは,未結合のトランスクリプトを生成するが,刺激なしには成熟したmRNAを生成しない.
- PRG誘導は,P-TEFb募集による信号依存の転写延長とmRNA処理によって調節される.
- Brd4は,PRGのプロモーターで誘導的に獲得されたH4K5/8/12Acを認識することによって,P-TEFbを勧誘する.
結論:
- PRGの許容的な構造は,コアプレッサー複合体による彼らのユニークな基礎状態の調節を促進します.
- この構造は,また,様々な細胞タイプでPRGの急速な誘導を可能にします.
- Brd4媒介によるP-TEFbの徴募は,PRGの迅速な活性化に不可欠である.
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