ジゴティックな父親のゲノム脱メチル化におけるエルンゲーター複合体の役割

Yuki Okada¹, Kazuo Yamagata, Kwonho Hong

¹Howard Hughes Medical Institute, Chapel Hill, North Carolina 27599-7295, USA.

Nature

|January 8, 2010

まとめ

研究者らは,エルンガーター複合体の構成要素であるElp3を,哺乳類における父親のDNA脱メチル化に不可欠であると特定しました. この発見は,受精後の重要なゲノム再プログラムに光を当てています.

科学分野:

エピジェネティクスエピジェネティクス
ゲノミクスゲノミクスとは
哺乳類の発達について

背景:

哺乳類の胚の発達は受精で始まり,その後に必須のゲノム再プログラムが行われます.
父のゲノム脱メチル化は,細菌から体細胞転写への移行にとって重要な出来事ですが,責任のある要因は依然として捉え難いままです.

研究の目的:

哺乳類のジゴトにおける父親のDNA脱メチル化に起因する分子因子を特定する.
この重要な再プログラミングイベントにおける延長器複合体の役割を調査する.

主な方法:

生細胞画像システムの開発で,シゴトの父親のDNAメチル化を監視する.
ショートインターフェリングRNA (siRNA) 媒介のノックダウンが,マウスジゴトの候補遺伝子を駆除する.
レポーター結合測定,免疫染色,およびビスルフィット配列解析を用いた脱メチル化の評価.
特定のドメインの変異を有するElp3変異体の機能分析.

主要な成果:

Elp3 (延長器複合体成分) のノックダウンにより,父親のDNA脱メチル化が著しく低下しました.
他の延長器成分 (Elp1,Elp4) の枯渇は,同様に脱メチル化に影響しました.
Elp3のSAMラジカルドメインは,HATドメインではないが,脱メチル化プロセスに不可欠であることが判明した.

結論:

エロングエーター複合体,特にElp3は,ジゴティック父性ゲノム脱メチル化において重要な役割を果たします.
父のDNA脱メチル化には,ELP3.3のSAM基域に依存する反応が伴う可能性が高い.

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