多能転写回路におけるTFIIDの中心的な役割
W W M Pim Pijnappel1, Daniel Esch, Marijke P A Baltissen
1Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Nature
|March 19, 2013
まとめ
一般的な転写因子TFIIDは,胚性幹細胞の同一性を維持し,体細胞を誘発性多能幹細胞に再プログラムするために重要である. TFIIDレベルを上げることで,再プログラミングの効率が著しく向上します.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
背景:
- 胚性幹細胞 (ES) は多能性を持ち,オープンクロマチンと高転写によって特徴付けられ,Oct4,Sox2,Klf4,c-Myc (OSKM),Nanog.のようなコア因子によって維持されます.
- OSKM因子の強制発現は,体細胞を誘発性多能幹細胞 (iPSC) に再プログラムすることができます.
- トランスクリプション因子IID (TFIID) 複合体のような基礎トランスクリプション機構が,多能性および再プログラミングを維持する役割は十分に理解されていません.
研究 の 目的:
- ES細胞の多能状態を維持するTFIID複合体の役割を調査する.
- TFIIDが,体細胞をiPSCへと再プログラムすることに与える影響を決定する.
主な方法:
- マウスのES細胞におけるTFIIDサブユニットのノックダウン.
- 多能遺伝子回路に対するTFIIDノックダウンの効果を評価する.
- TFIID操作を伴い,または伴わないiPSCへのフィブロブラスト再プログラミングの効率を評価する.
主要な成果:
- TFIIDのノックダウンは,ES細胞の多能回路を混乱させ,体細胞の再プログラミングを阻害する.
- TFIIDサブユニットとOSKM因子は,多能細胞における安定した転写に不可欠なフィードフォワードループを形成する.
- TFIIDサブユニットの一時的な表現は,再プログラミングの効率を大幅に高めます.
結論:
- TFIIDは,トランスクリプション・ファクター媒介による再プログラミングの重要な構成要素です.
- TFIIDは,再プログラミング中に細胞のアイデンティティを確立し維持する上で重要な役割を果たします.
- TFIIDのような転写複合体は,細胞の可塑性に貢献し,様々な細胞状態への再プログラムを促進します.
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02:23Master Transcription Regulators
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