5mCから5hmCへの変換,ES細胞の自己再生,内細胞質量指定におけるTetタンパク質の役割

Shinsuke Ito¹, Ana C D'Alessio, Olena V Taranova

¹Howard Hughes Medical Institute.

Nature

|July 20, 2010

まとめ

Tetタンパク質はDNA脱メチル化を触媒化し,5-メチルサイトシンを5-ヒドロキシメチルサイトシンに変換する. Tet1は,胚の幹細胞のアイデンティティと適切な胚の発達を維持するために不可欠です.

科学分野:

エピジェネティクスエピジェネティクス
分子生物学は分子生物学である.
発達生物学発達生物学について

背景:

DNAメチル化は重要なエピジェネティック改変ですが,脱メチル化酵素はほとんど知られていませんでした.
以前の研究では,ヒトのTET1がDNA脱メチル化を媒介する可能性があると示唆されていた.
Tetタンパク質の酵素活性と生物学的役割は,まだ完全に解明されていない.

研究の目的:

DNA脱メチル化におけるマウスTETタンパク質の酵素活性を調査する.
胚性幹細胞の維持と分化におけるTet1の役割を決定する.
胚の発達初期におけるTet1の機能を調査する.

主な方法:

酵素測定法で,DNA上のTetタンパク質の活性をテストする.
Tet1はマウスの胚性幹細胞でのノックダウン実験を行った.
ナノグの遺伝子発現とプロモーターメチレーションの分析.
植入前のマウス胚におけるノックダウン研究.

主要な成果:

ネズミの3つのTETタンパク質 (Tet1, Tet2, Tet3) はすべて,5-メチルサイトシン (5mC) を5-ヒドロキシメチルサイトシン (5hmC) に変換することが示されました.
胚性幹細胞におけるTet1ノックダウンは,ナノグのダウンレギュレーションとナノグプロモーターのハイパーメチル化につながった.
植入前の胚におけるTet1ノックダウンは,トロフェクトダームの分化が増加した結果となった.

結論:

Tetタンパク質は,DNAを脱メチル化する酵素活性を持っています.
Tet1は,ナノゲル調節によるマウスの胚性幹細胞の多能性を維持する上で重要な役割を果たしています.
Tet1は,マウスの初期の胚形成の間に適切な細胞運命を特定するために不可欠です.

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