在组织特异性白蛋白基因表达中,cis作用促进元素的作用
P Maire1, J Wuarin, U Schibler
1Département de Biologie Moléculaire, Sciences II, Geneva, Switzerland.
Science (New York, N.Y.)
|April 21, 1989
概括
与小鼠白蛋白基因促进体结合的核蛋白显示出组织特异转录的层次结构. 肝细胞核因子1 (HNF-1) 和CCAAT/增强剂结合蛋白 (C/EBP) 位点强烈激活转录,而NF-Y位点显示较低,不太特定的激活.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 鼠标白蛋白基因促进体含有多个核蛋白结合部位,对于调节基因表达至关重要.
- 了解这些结合位点的等级功能是破译组织特异性转录的关键.
- 之前的研究已经确定了促进体区域内的几个蛋白质结合部位.
研究的目的:
- 研究小鼠白蛋白基因促进体内不同核蛋白结合位点的等级重要性.
- 确定特定结合位点,如HNF-1,C/EBP和NF-Y在组织特异性白蛋白基因转录中的作用.
- 阐明这些促进元素的差异激活潜力和特异性.
主要方法:
- 在体外转录测试使用模板与突变或聚合的白蛋白促进元素.
- 利用肝脏和脏组织的核提取物来评估特定组织的结合和激活.
- 基于特定蛋白质结合部位的修改,对转录水平的比较分析.
主要成果:
- 建立了影响白蛋白基因转录的蛋白质结合部位的层次结构.
- 肝细胞核因子1 (HNF-1) 和CCAAT/增强剂结合蛋白 (C/EBP) 的结合部位表现出强烈的,组织特异性的激活.
- 核因子Y (NF-Y) 的结合部位表现出较低的激活潜力和较低的组织特异性,在肝脏和脏提取物中功能相似.
- 其他已识别的元素作为相对较弱的激活器位点.
结论:
- 专基因促进元件的功能层次决定了组织特异性的转录.
- HNF-1和C/EBP是肝脏特异性白蛋白基因表达的关键调节剂.
- 与HNF-1和C/EBP相比,NF-Y有助于专蛋白基因转录,具有更广泛的组织适用性.
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