Xist 調節と多能性の分子結合
Pablo Navarro1, Ian Chambers, Violetta Karwacki-Neisius
1Institut Pasteur, Unité de Génétique Moléculaire Murine, CNRS, URA2578, F-75015, Paris, France.
Science (New York, N.Y.)
|September 20, 2008
まとめ
多能性因子であるNanog,Oct3/4,Sox2は,胚性幹細胞におけるXistRNAの蓄積を抑制する. この結合は,X染色体不活性化再プログラムが胚形成中の多能性制御と一致することを保証する.
科学分野:
- 発達生物学 発達生物学とは
- エピジェネティクス エピジェネティクス
- 幹細胞生物学 幹細胞生物学
背景:
- X染色体不活性化 (XCI) は,雌性哺乳類における用量補償に不可欠である.
- プリントされたXCIの逆転は,マウスの胚形成中に内部の細胞群で起こります.
- Xist RNAの抑制により,父親のX染色体の再活性化が始まります.
研究 の 目的:
- プラリポテンシーとシストの調節を結びつける分子メカニズムを調査する.
- 胚性幹細胞 (ES) のXist発現を制御する要因を特定する.
主な方法:
- 染色体免疫降水 (ChIP) は,因子結合を評価する.
- ワイルドタイプおよびナノグヌールES細胞におけるXist RNAレベルの分析.
- Xist発現に対するプラリポテンシー因子放出の影響を調査する.
主要な成果:
- Nanog,Oct3/4,およびSox2は,無差別化されたES細胞のXistイントロン1に結合する.
- ナノグの喪失は,適度な,可逆的なXistのアップレギュレーションにつながる.
- この3つの因子の結合が失われると,XistRNAが急速に蓄積する.
結論:
- 主要な多能性因子 (Nanog, Oct3/4, Sox2) は,Xist.を抑制するために協力します.
- このメカニズムは,X不活性化再プログラムと多能性維持を組み合わせている.
- 胚形成の際に全ゲノムにわたる表遺伝的再プログラミングの調整制御を保証する.
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