REST:哺乳類のサイレンサータンパク質で,ナトリウムチャネル遺伝子発現をニューロンに制限する
J A Chong1, J Tapia-Ramírez, S Kim
1Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794-5230.
Cell
|March 24, 1995
まとめ
新しい転写因子,抑制要素静止転写 (REST) は,非ニューロン細胞におけるII型ナトリウムチャネル遺伝子を静止させます. このメカニズムは,神経細胞の遺伝子が神経系内でどのように特異的に発現するかを説明する.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- タイプIIの電圧依存ナトリウムチャネル遺伝子は,ニューロンの機能に極めて重要です.
- その発現は通常,ニューロンに限定されるが,その基礎となる規制メカニズムは完全に理解されていない.
研究 の 目的:
- II型電圧依存ナトリウムチャネル遺伝子のニューロン特異的発現に起因する調節因子を特定する.
- このプロセスにおける特定のサイレンサー要素とその関連する転写因子の役割を明らかにする.
主な方法:
- 転写因子REST (レプレッサーエレメントサイレンストランスクリプション) をコードするcDNAのクローン.
- ニューロンの細胞と非ニューロンの細胞タイプにおける再結合RESTタンパク質と支配的-負のRESTを用いた機能分析.
- 開発中のマウス胚におけるRESTトランスクリプト分布の分析.
主要な成果:
- 転写因子であるRESTは,II型ナトリウムチャネル遺伝子を調節するサイレンサー要素と結合することを特定しました.
- 生まれながらのRESTが欠けているニューロン細胞における再結合RESTサイレントレポーター遺伝子の発現.
- 主要負のRESTは,非ニューロン細胞の静止を緩和した.
- RESTトランスクリプトは,発達中のマウスの胚の神経系以外の組織で広く発見されました.
結論:
- 転写因子RESTは,非ニューロン細胞におけるII型ナトリウムチャネル遺伝子発現を抑制する上で重要な役割を果たします.
- タイプIIナトリウムチャネル遺伝子のニューロン発現は,RESTによって非ニューロン細胞で積極的に抑制されるデフォルト経路を表す可能性があります.
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