这种Xenopus Wnt效应器XTcf-3与Groucho相关的转录抑制剂相互作用
J Roose1, M Molenaar, J Peterson
1Department of Immunology, University Hospital, Utrecht, The Netherlands.
Nature
|October 23, 1998
概括
转录因子Tcf/Lef与Groucho抑制剂相互作用,调节基因表达. 阿马迪略和格鲁乔之间的这种平衡决定了Tcf在发育过程中的基因活性.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 基因规则 基因规则
背景情况:
- Tcf/Lef转录因子通过招募Armadillo/β-catenin作为协同激活剂来调解无翼/Wnt信号.
- 有证据表明,TCF因子也可以在各种模型生物中作为转录抑制剂发挥作用.
研究的目的:
- 研究TCF因素与Groucho家族成员之间的相互作用.
- 确定Groucho蛋白在TCF介导的转录调节中的作用.
- 阐明阿马迪略和格鲁乔在控制TCF基因表达中的平衡.
主要方法:
- 测试TCF因子和Groucho蛋白之间的物理相互作用.
- 使用合成TCF记者基因进行过渡性转染试验.
- 在体内研究涉及微注射到Xenopus胚胎,以评估转录抑制和发育影响.
主要成果:
- Tcf因子与Groucho家族成员进行物理相互作用,这些因子是已知的转录抑制剂.
- 克塞诺普斯Groucho的同类XGrg-4抑制了TCF介导的转录,而XGrg-5则增强了它.
- 在Xenopus胚胎中,XGrg-4抑制了内源性TCF基因 (Siamois,Xnr-3) 并引起腹部化;XGrg-5抵消了这些影响.
结论:
- 通过TCF介导的基因表达是通过联合激活剂Armadillo和抑制剂Groucho之间的平衡来调节的.
- 格劳乔蛋白质在调节Tcf/Lef活性方面发挥着至关重要的作用,根据特定的格劳乔家族成员,它们起到抑制剂或增强剂的作用.
- 这种调节平衡对于正常的胚胎发育至关重要,正如对Xenopus胚胎生成的影响所证明的那样.
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