AF9 YEATSドメインはヒストンアセチル化とDOT1L媒介のH3K79メチル化をリンクしている
Yuanyuan Li1, Hong Wen2, Yuanxin Xi3
1Collaborative Innovation Center for Biotherapy, MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Cell
|November 24, 2014
まとめ
AF9 YEATSドメインはヒストンのアセチル化,特にH3K9ac.ac.を認識しています. この発見は,ヒストンのアセチル化と遺伝子転写の調節を結びつける上で極めて重要な新しいアセチリシンリーダーを明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- 構造生物学 構造生物学とは
背景:
- ヒストンの改変が遺伝子発現を調節する.
- メチル化と比較してヒストンアセチル化を認識するタンパク質モジュールはほとんどありません.
- アセチリリシンリーダーの理解は,遺伝子調節の解読に不可欠です.
研究 の 目的:
- ヒストンアセチレーションを認識する新しいタンパク質モジュールを識別する.
- AF9 YEATSドメインによるアセチリジンの認識の構造的基礎を解明する.
- ヒストンアセチル化と遺伝子転写を結びつけるAF9の機能的役割を調査する.
主な方法:
- AF9 YEATSドメインとアセチルヒストンの相互作用を評価するためのタンパク質-リガンド結合測定法.
- AF9 YEATSドメインの構造を決定するX線結晶学.
- クロマチン免疫プレシピテーションシーケンシング (ChIP-seq) によって,AF9とH3K9のアセチル化ゲノム全体をマッピングする.
主要な成果:
- AF9 YEATSドメインはH3K9アセチル化に強く結合し,H3K27およびH3K18アセチル化に少なからず結合する.
- 構造的研究により,AF9 YEATSドメインによるアセチリジンの読み取りのための新しい"サンドイッチング"ケージメカニズムが明らかになりました.
- AF9およびH3K9アセチル化の全ゲノム規模のコロカライゼーションが観察され,DOT1LリクルートおよびH3K79メチル化に影響を与えました.
結論:
- YEATSドメインは,アセチリリシン結合モジュールである.
- AF9はヒストンアセチル化 (H3K9ac) をDOT1L媒介によるH3K79メチル化と結びつける.
- これは,転写制御メカニズムに関する新しい洞察を提供します.
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