増強剤の活性化によるプロモーター近接停止放出のPAF1調節
Fei Xavier Chen1, Peng Xie2, Clayton K Collings1
1Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Science (New York, N.Y.)
|September 2, 2017
まとめ
RNAポリメラーゼII (Pol II) の停止は遺伝子発現を調節する. Pol II関連因子1 (PAF1) タンパク質は,停止した遺伝子からのPol II放出を制御し,強化剤の活性を抑制する.
科学分野:
- 分子生物学
- 遺伝子規制
- トランスクリプション・コントロール
背景:
- 多細胞生物 (メタゾーン) の遺伝子発現は,RNAポリメラーゼII (Pol II) のプロモーター近接停止と放出に依存する.
- Pol II関連因子1 (PAF1) は以前,生産的伸縮へのPol II放出の調節剤として特定されました.
- PAF1が転写増強剤を調節する正確な役割と,Pol IIの動態に対するその影響は不明でした.
研究 の 目的:
- 転写強化剤におけるPAF1の機能を調査する.
- 強化剤とのPAF1の相互作用がPol IIの停止と放出にどのように影響するかを決定する.
- PAF1 調節剤が遺伝子発現を制御するメカニズムを解明する.
主な方法:
- 転写強化剤におけるPAF1占有率の分析
- CRISPR媒介による PAF1 調節剤のノックアウト
- 分子生物学技術を用いた標的遺伝子プロモーターにおけるPol IIの停止と放出ダイナミクスの評価.
主要な成果:
- PAF1は,転写強化剤を占め,これらの調節要素のサブセットの過剰活性化を抑制することが判明しました.
- PAF1の喪失は,その標的強化剤の活性化につながり,その後,近くの遺伝子プロモーターから一時停止したPol IIを放出します.
- PAF1 調節された増強剤の破壊は,初期プロモーターの停止に影響を及ぼさず,標的遺伝子のPol II 放出を特異的に阻害しました.
結論:
- 転写強化剤は,停止したプロモーターからのPol II放出を制御することによって,遺伝子発現を調節する上で重要な役割を果たします.
- PAF1は重要な調節剤として作用し,強化剤を結合させ,その活動を抑制し,それによってPol IIの放出に影響を与えます.
- このPAF1依存の増強メカニズムは,一時停止から延長への移行を微調整することによって,遺伝子発現に対する特定の制御層を提供します.
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