マスター転写因子は,TGF-βシグナル伝達に対する細胞タイプ特有の反応を決定する
Alan C Mullen1, David A Orlando, Jamie J Newman
1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell
|November 1, 2011
まとめ
Oct4,Myod1,PU.1のようなマスター転写因子は,Smad3が結合する場所を決定し,成長因子β (TGF-β) 信号伝達を変換する細胞特有の反応を制御します.
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.
- 遺伝学 遺伝学とは
背景:
- 成長因子β (TGF-β) 信号の変換は,多様な細胞機能に不可欠です.
- 転写因子Smad2およびSmad3 (Smad2/3) は,TGF-βシグナル伝達を媒介する.
- TGF-βシグナル伝達は,細胞タイプによって異なる細胞反応を誘発する.
研究 の 目的:
- Smad2/3が細胞型特異的なゲノム占有率を達成する方法を調査する.
- Smad3結合を誘導するマスタートランスクリプション因子の役割を特定する.
- 細胞特異のTGF-β応答の背後にあるメカニズムを理解する.
主な方法:
- 異なる細胞タイプ (胚性幹細胞,ミオチューブ,プロB細胞) でのSmad3の全ゲノム占有率分析.
- Smad3結合のためのマスター転写因子の要件を決定するためのアッセイ.
- マスター転写因子によって結合される遺伝子に対するTGF-βシグナル伝達効果の分析.
- 非筋肉細胞におけるマスター転写因子 (Myod1) の実験誘導.
主要な成果:
- Smad3は,細胞型特異のマスター転写因子:ESCのOct4,筋管のMyod1,プロB細胞のPU.1と共にゲノムを占有している.
- マスター転写因子はSmad3のゲノム結合に不可欠です.
- TGF-βシグナル伝達は,主にこれらのマスター転写因子によって占有される遺伝子に影響を与えます.
- 非筋肉細胞にMyod1を誘導すると,Smad3の結合をMyod1に関連した部位にリダイレクトします.
結論:
- 細胞型特異的なマスタートランスクリプションファクターは,Smad2/3.3のゲノム標的を決定する.
- これらのマスターファクターは,細胞特異のTGF-βシグナル伝達結果の主要なオーケストレーターです.
- このメカニズムは,保存されたシグナル伝達経路が多種多様な細胞反応を生成する方法を説明します.
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