亜鉛指の遺伝子Krox20は,後頭脳のセグメンテーション中にHoxB2 (Hox2.8) を調節する
M H Sham1, C Vesque, S Nonchev
1MRC Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London.
Cell
|January 29, 1993
まとめ
Krox20転写因子は,HoxB2の遺伝子発現を直接調節し,形質的変化が起こる前に後脳セグメントのアイデンティティを確立します. この発見は,Krox2020を明らかにしています.
科学分野:
- 発達生物学 発達生物学について
- 神経科学は神経科学である.
- 遺伝学 遺伝学とは
背景:
- クロックス20およびホックス遺伝子を含む後脳におけるセグメント限定遺伝子発現は,形態学的セグメント化に先行する.
- これらの転写因子は,ロンボメリックセグメントのアイデンティティを確立する上で重要な役割を果たすという仮説があります.
研究 の 目的:
- 後頭脳のセグメンテーション中にKrox20とHoxB2の規制関係を調査する.
- HoxB2ロンボメール特異的発現に関与する特定の規制要素と転写因子を特定する.
主な方法:
- HoxB2遺伝子の上流のエンハンサー領域の識別と特徴付け.
- ホックスB2増強剤内のクロックス20結合部位の分析 in vitroおよびin vivoアッセイを用いて.
- HoxB2増強剤の機能とKrox20の役割を評価するために,トランスジェニックマウスの生成と分析.
主要な成果:
- HoxB2の上流にある特定の増強剤領域が特定され,ロンボメア3および5 (r3/r5) の発現が認められた.
- この増強剤には,3つのクロックス20結合部位が含まれており,これはインビトロのタンパク質結合とインビボのロンボメア限定発現に不可欠です.
- トランスジェニックマウスにおけるエクトピックKrox20発現は,HoxB2r3/r5増強剤を含むレポーター構造体を活性化させ,Krox20のトランザクティベーション能力を確認した.
結論:
- Krox20は HoxB2 増強剤に直接結合し,その発現をロンボメール特異的な方法で調節する.
- Krox20は,トランスクリプションカスケードで上流に作用し,後脳分割中にHoxB2の発現を直接制御します.
- これらの発見は,後脳セグメントのアイデンティティ確立の基礎にある重要な分子メカニズムを明らかにします.
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