CtBP共抑制体複合体によって媒介される協調ヒストンの改変

Yujiang Shi¹, Jun-ichi Sawada, Guangchao Sui

¹Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. yang_shi@hms.harvard.edu

Nature

|April 18, 2003

まとめ

C末端結合タンパク質 (CtBP) 複合体は,DNAターゲティングとヒストン改変を通じて遺伝子抑制を媒介する. このメカニズムは,腫瘍形成と動物の発達における役割において極めて重要です.

科学分野:

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
癌生物学癌生物学について

背景:

転写共抑制体C端結合タンパク質 (CtBP) は腫瘍発生と動物の発達に関与しています.
CtBPは,PXDLSモチーフを持つ転写因子を介してDNAに採用されますが,その正確な機能は不明です.

研究の目的:

CtBP媒介による遺伝子抑制の分子メカニズムを特定する.
腫瘍発生におけるCtBPの役割を調査する.

主な方法:

遺伝子ターゲティングとヒストン改変能力を持つCtBP複合体の特定.
RNA媒介による干渉により,CtBP発現および関連する活動を阻害する.
E-カデリンのプロモーターおよびレポーター遺伝子アッセイにおけるヒストンの改変の分析.

主要な成果:

遺伝子ターゲティングとヒストンの改変を可能にするCtBP複合体が特定されました.
CtBPの阻害により,E-cadherinプロモーターのヒストンの変化が起きました.
CtBPを抑制すると,E-カデリンのプロモーター活性が増加します.

結論:

CtBPは,調整された遺伝子ターゲティングとヒストンの修正を通じて,転写抑制を媒介する.
これらの発見は,CtBPが腫瘍発生に関与するメカニズムを明らかにしています.

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