ATMに関連するTra1サブユニットとの直接アクティベーター相互作用によってHAT複合体のリクルート
1Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, Department of Chemistry, The Pennsylvania State University, 306 Althouse Laboratory, University Park, PA 16802, USA.
Science (New York, N.Y.)
|June 26, 2001
まとめ
酸性転写活性化剤は,ヒストンアセチルトランスフェラーゼ複合体SAGAとNuA4.4に共通するサブユニットであるTra1pに直接結合する. この相互作用を妨害すると,遺伝子特異の転写とヒストンのアセチル化が損なわれます.
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:
- SAGAやNuA4のようなヒストンアセチルトランスフェラーゼ (HAT) 複合体は,遺伝子転写に不可欠である.
- 特定の遺伝子プロモーターにHATの活性を誘導することは,重要な規制ステップです.
- 転写活性化剤とHATの相互作用は,この募集に不可欠です.
研究 の 目的:
- 転写活性化剤とSAGAおよびNuA4HAT複合体との直接的な相互作用を調査する.
- アクティベータ結合に関与するSAGAとNuA4の特定のサブユニットを特定する.
- アクティベータとHATの相互作用を妨害する機能的結果を解明する.
主な方法:
- 相互作用するタンパク質を特定するために,アフィニティクロマトグラフィーを用いた.
- 直接的な相互作用を確認するために,写真クロスリンクのラベル転送実験が行われました.
- サイト指向型変異は,特定のタンパク質ドメインの役割を研究するために使用されました.
主要な成果:
- 酸性転写活性化剤は,SAGAとNuA4.4の共有サブユニットであるTra1pと直接相互作用する.
- Tra1pのCOOH末端の変異により,アクティベーター結合が廃止された.
- これらの変異は,遺伝子特異の転写欠陥を引き起こし,プロモーター特異のヒストンアセチル化を減少させた.
結論:
- Tra1タンパク質は,SAGAおよびNuA4 HAT複合体と相互作用する転写活性化剤の共通で重要な標的である.
- Tra1pとの直接的な相互作用は,HATの活性と,その後の遺伝子活性化の募集に不可欠です.
- この研究は,HAT複合体による転写の調節に関するメカニズム的洞察を提供します.
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