時間解像度分析は,CBP/p300アセチロームの急速な動態と広範な範囲を明らかにする
Brian T Weinert1, Takeo Narita1, Shankha Satpathy1
1Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Cell
|May 29, 2018
まとめ
研究はCBPとp300によって調節されるアセチル化部位をマッピングし,これらの酵素に依存する急速なターンオーバーとダイナミックな遺伝子発現ネットワークを明らかにした. この研究は,CBP/p300機能と標的抑制剤の理解を助長する.
科学分野:
- 生物化学
- 分子生物学
- エピジェネティクス
背景:
- 転写共同活性化剤CBP (CREB結合タンパク質) とp300は遺伝子調節に不可欠である.
- 彼らの役割はタンパク質アセチル化を触媒化し,これは重要な翻訳後の修正である.
研究 の 目的:
- CBP/p300によって規制されたアセチル化部位を包括的にマッピングする.
- これらのアセチル化サイトの動的ターンオーバーを調査する.
- 遺伝子発現ネットワークにおけるCBP/p300媒介アセチル化の役割を理解する.
主な方法:
- 定量プロテオミクスは,アセチル化部位を特定し定量化するために使用されました.
- CBP/p300特有の触媒およびブロモドメイン阻害剤を使用した.
- 遺伝子ノックアウト戦略が実施された.
- 時間の解析によるアセチローム分析が行われました.
主要な成果:
- 何千ものアセチル化部位がマッピングされ,ヒストンの改変と調節タンパク質の部位も含まれていた.
- サイトのサブセットは,ダイナミックなアセチル化/脱アセチル化バランスを示す,急速なアセチル化ターンオーバー (<30分) を示した.
- 遺伝子発現分析により,急速なCBP/p300アセチル化に依存するネットワークが明らかになった.
結論:
- CBP/p300は,ダイナミックなターンオーバーを持つ幅広いアセチル化サイトを制御します.
- CBP/p300による急速なアセチル化は,運動能力のある遺伝子発現ネットワークにとって不可欠である.
- この発見は,CBP/p300機能と阻害剤発達の研究のための枠組みを提供する.
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