ヒストンH2Aにおけるグルタミンメチル化は,RNAポリメラーゼI専用の改変である
Peter Tessarz1, Helena Santos-Rosa1, Sam C Robson1
11] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Nature
|December 20, 2013
まとめ
研究者らは,リボソームのDNA転写の調節に不可欠なH2Aのグルタミンメチル化という新しいヒストンの改変を発見しました. このエピジェネティックマークはRNAポリメラーゼIを特異的に標的にし,FACT複合体の核細胞との相互作用に影響を与えます.
科学分野:
- エピジェネティクスと分子生物学
- クロマチンの生物学
- 核細胞機能について
背景:
- 核細胞は,DNAプロセスに影響を与える様々な翻訳後の修正を受けます.
- ヒストンの改変は,遺伝子発現とクロマチンの構造の重要な調節因子である.
研究 の 目的:
- 新しいヒストンの改変を特定し特徴づけるために:グルタミン甲基化.グルタミン甲基化.
- この変異の原因となる酵素とその細胞の位置を決定する.
- DNA転写の調節におけるグルタミン甲基化の機能的役割を明らかにする.
主な方法:
- イーストとヒトの細胞におけるヒストンH2Aに対するグルタミンメチル化の識別.
- イーストの遺伝子 (Nop1) とヒトのオルトローグ分析 (フィブリラーリン) を用いた酵素識別.
- H2A Q105メチル化 (H2AQ105me) の特定検出のための抗体生成.
- FACT複合体の相互作用を研究するためのクロマチンの免疫プレシピテーションおよびインビトロ結合アッセイ.
主要な成果:
- 新しいヒストンの改変であるグルタミンメチル化 (酵母H2AにおけるQ105) が特定されました.
- Nop1とフィブリラーリンは,酵母とヒトの細胞におけるメチルトランスファーゼとして特定されました.
- この改変は,35SリボソームDNA (rDNA) のロクスの上の核内にのみ濃縮されている.
- H2A Q105メチル化はヒストンチャペロンFACT複合体の結合を調節する.
- Q105またはFACT成分における突然変異は,ヒストンの組み込みとrDNAの転写を変化させます.
結論:
- H2Aのグルタミンメチル化は,RNAポリメラーゼIに特異的な最初のヒストンマーカーである.
- このエピジェネティックマークは,核個体とのFACT複合体の相互作用を調節する.
- 核内のリボソームDNA転写とクロマチンの動態を制御する上で重要な役割を果たします.
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