指基因Krox20在后脑细分过程中调节HoxB2 (Hox2.8)
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
概括
Krox20转录因子直接调节HoxB2基因表达,在发生形态变化之前建立后脑部分身份. 这一发现揭示了Krox2020
科学领域:
- 发展生物学 发展生物学
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
背景情况:
- 在后脑中,包括Krox20和Hox基因在内的细分受限基因表达在形态细分之前.
- 假设这些转录因子在建立染色体片段身份方面发挥着至关重要的作用.
研究的目的:
- 在后脑细分过程中调查Krox20和HoxB2之间的调控关系.
- 为了确定参与HoxB2染色体特异表达的特定调节元素和转录因子.
主要方法:
- 在HoxB2基因上游的增强器区域的识别和表征.
- 在HoxB2增强剂内的Krox20结合部位的分析,使用体外和体内测试.
- 转基因小鼠的生成和分析,以评估HoxB2增强剂的功能和Krox20的作用.
主要成果:
- 确定了HoxB2上游的一个特定的增强剂区域,赋予了染色体3和5 (r3/r5) 的表达.
- 这种增强剂含有三个Krox20结合位点,对于体外蛋白质结合和体内血红蛋白受限表达都至关重要.
- 转基因小鼠的异卵性Krox20表达激活了含有HoxB2r3/r5增强剂的记者结构,证实了Krox20的交换活化能力.
结论:
- 克罗克斯20直接与HoxB2增强剂结合,并以一种与红色素特异的方式调节其表达.
- 在转录级联中,Krox20在上游作用,在后脑细分过程中直接控制HoxB2的表达.
- 这些发现阐明了一个关键的分子机制,它是后脑部分身份建立的基础.
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