TGF-βがマスターレギュレータにアクセスするためのバランスのとれたクロマチンのプラットフォーム
Qiaoran Xi1, Zhanxin Wang, Alexia-Ileana Zaromytidou
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|December 27, 2011
まとめ
ノダル信号は,平衡したヒストンマークH3K9me3.3.をターゲットにすることで,胚性幹細胞の分化を活性化します. この相互作用は,重要なタンパク質を誘発し,細胞の運命を決定するマスターレギュレータの活性化を可能にします.
科学分野:
- 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
- 分子シグナリング
背景:
- 差別化のマスターレギュレータは,特定のクロマチンのマークによって静止され,アクティベーションの準備が整っています.
- 結節TGF-βなどの細胞外信号は,静止状態から活性状態への移行を誘発することができます.
研究 の 目的:
- 結節TGF-β信号が哺乳類の胚性幹細胞の分化を引き起こすメカニズムを解明する.
- 特定のヒストンマークやタンパク質複合体の,分化レギュレータの活性化における役割を調査する.
主な方法:
- 結晶構造を用いたタンパク質-DNA相互作用の分析.
- TRIM33-Smad2/3複合体のヒストンペプチドへの結合を調査した.
- HP1γの移位とPol IIの徴集を研究した.
主要な成果:
- ノダル信号は,平衡のヒストンマークH3K9me3を利用して,幹細胞の分化を開始します.
- TRIM33 PHD-Bromoカセットは,H3K9me3とH3K18acに結合し,差別化規制器へのアクセスを容易にします.
- この相互作用はHP1γを位移させ,Smad4-Smad2/3の徴募とPol IIの活性化を可能にし,Smad4はH3K18のアセチル化を強化する.
結論:
- ノダルシグナル伝達は,H3K9me3を,幹細胞の微分化の安定したマスターレギュレータを活性化するためのプラットフォームとして使用します.
- ヒストンの改変とタンパク質複合体の相互作用は,微分化中のクロマチンのアクセシビリティと遺伝子活性化の動的変化に不可欠です.
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