Xenopus Wnt エフェクタ XTcf-3 は,Grouchoに関連する転写抑制剤と相互作用する
J Roose1, M Molenaar, J Peterson
1Department of Immunology, University Hospital, Utrecht, The Netherlands.
Nature
|October 23, 1998
まとめ
転写因子Tcf/Lefは,Groucho抑制剤と相互作用して,遺伝子発現を調節する. アーマディッロとグルーチョのバランスは,発達過程におけるTCF標的遺伝子の活動を決定する.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学とは
- 遺伝子規制 遺伝子規制
背景:
- Tcf/Lef転写因子は,Armadillo/β-cateninを共同活性化剤として採用することによって,Wingless/Wntシグナリングを媒介する.
- 証拠によると,Tcf因子は,様々なモデル生物の転写抑制剤としても機能することが示唆されています.
研究 の 目的:
- Tcf要因とGrouchoファミリーメンバーの相互作用を調査する.
- Tcf媒介による転写調節におけるGrouchoタンパク質の役割を決定する.
- Tcf標的遺伝子発現の制御におけるアーマディヨとグルーチョのバランスを明らかにする.
主な方法:
- Tcf因子とGrouchoタンパク質の間の物理的な相互作用を測定する.
- 合成TCFレポーター遺伝子を用いたトランジント・トランスフェクション・アッセイ.
- Xenopus胚へのマイクロ注入を伴うin vivo研究で,転写抑制と発達効果を評価する.
主要な成果:
- Tcf因子は,トランスクリプション抑制剤として知られるGrouchoファミリーのメンバーと物理的に相互作用します.
- Xenopus Grouchoの同型XGrg-4はTCF媒介の転写を阻害し,XGrg-5はそれを強化した.
- XGrg-4は内生的なTCF標的遺伝子 (サイアモス,Xnr-3) を抑制し,Xenopus胚の腹部化を引き起こした;XGrg-5はこれらの効果を相殺した.
結論:
- Tcf媒介の遺伝子発現は,共同活性化剤であるArmadilloと抑制剤であるGrouchoのバランスによって調節される.
- グルーチョのタンパク質は,Tcf/Lefの活性を調節する上で重要な役割を果たし,特定のグルーチョファミリーのメンバーによって抑制剤または強化剤として作用します.
- この調節バランスは,Xenopusの胚形成への影響によって示されているように,正常な胚の発達に不可欠です.
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