ヒトのPRC2とその共因子AEBP2とJARID2の構造
Vignesh Kasinath1,2, Marco Faini3, Simon Poepsel1,2
1QB3 Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|January 20, 2018
まとめ
ポリコンブ抑制複合体2 (PRC2) メチル化が発達に不可欠である. Cryo-EM構造は,JARID2とAEBP2がヒストンの尾を模倣してPRC2の活動を調節する方法を明らかにし,複雑な構造と調節に関する洞察を提供します.
科学分野:
- エピジェネティクスと遺伝子調節
- 構造生物学
- 発達 の 分子 機構
背景:
- ポリコンブ抑制複合体2 (PRC2) は,転写抑制の重要な表遺伝子マーカーであるヒストンH3リシン27メチル化を触媒化する.
- このメチル化は細胞の分化,発達,細胞のアイデンティティの維持に不可欠です.
- PRC2の活動不調は,発達障害と癌に関与しています.
研究 の 目的:
- 基礎状態と活性状態におけるヒトPRC2の高解像度構造を決定する.
- JARID2とAEBP2がPRC2の活動を調節する構造的メカニズムを解明する.
- PRC2の複雑なアーキテクチャとその規制に関する包括的な構造的な理解を提供すること.
主な方法:
- ヒトのPRC2複合体を視覚化するための冷凍電子顕微鏡 (冷凍EM).
- ベース状態とコファクター・バインド状態のPRC2の構造分析
- コファクター相互作用と機能的影響を確認するための生化学的測定.
主要な成果:
- 基礎状態と2つの異なる活性状態でヒトPRC2の冷凍-EM構造が報告されています.
- コファクターJARID2とAEBP2がヒストンH3尾を模倣してPRC2を調節することを実証した.
- JARID2は,メチル化されたH3尾を模倣してPRC2を刺激し,AEBP2は,改変されていないH3尾を模倣してRBAP48と相互作用する.
- SUZ12がPRC2全体の 安定化のための 鍵となるサブユニットだ
結論:
- 機能的に関連するPRC2複合体の完全なアーキテクチャを定義した.
- コファクター,ヒストンの尾,RNAによるPRC2の調節を理解するための構造的枠組みを提供した.
- 構造的な洞察は,PRC2に関連した病気の標的治療戦略の道を切り開きます.
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