DIVERSITY OF ALPHA-FETOPROTEIN GENE-EXPRESSION IN MICE IS GENERATED BY A COMBINATION OF SEPARATE ENHANCER ELEMENTS
DIVERSITY OF ALPHA-FETOPROTEIN GENE-EXPRESSION IN MICE IS GENERATED BY A COMBINATION OF SEPARATE ENHANCER ELEMENTS
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DOI：
10.1126/science.2432657
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发表时间：
1987-01-02
期刊：
影响因子：
56.9
通讯作者：
TILGHMAN, SM
中科院分区：
文献类型：
--
作者：
HAMMER, RE;KRUMLAUF, R;TILGHMAN, SM
小鼠甲胎蛋白（AFP）基因的5'侧翼区域包含一个组织特异性启动子和三个作为经典增强子的上游调控元件。当将克隆的DNA片段微量注射到受精卵中，将AFP基因引入小鼠基因组时，这些增强子中至少有一个被证明是组织特异性表达AFP基因所必需的。每种增强子都能在相应的组织中直接表达，即卵黄囊内脏内胚层、胎儿肝脏和胃肠道，但每种增强子对这三种组织的影响不同。这些差异可以解释AFP基因表达水平的组织特异性多样性。出生后肝脏和肠道中AFP基因转录的抑制，以及肝脏再生过程中其转录的重新启动，当引入的基因与增强子结构域一起或单独连接时，就会被模仿。因此，负责指导AFP转录的激活、抑制和再诱导的DNA序列元件包含在距离基因或两者5英寸的有限DNA片段中，并且在没有紧密相连的白蛋白基因的情况下起作用。
The 5'' flanking region of the mouse alpha-fetoprotein (AFP) gene contains a tissue-specific promoter and three upstream regulatory elements that behave as classical enhancers. At least one of these enhancers is now shown to be required for the tissue-specific expression of the AFP gene when it is introduced into the mouse genome by microinjection of cloned DNA fragments into fertilized eggs. Each enhancer can direct expression in the appropriate tissues, the visceral endoderm of the yolk sac, the fetal liver, and the gastrointestinal tract, but each exerts different influence in these three tissues. These differences may explain the tissue-specific diversity in the levels of expression characteristic of the AFP gene. The postnatal repression of transcription of the AFP gene in both liver and gut, as well as the reinitiation of its transcription during liver regeneration, is mimicked by the introduced gene when it is linked to the enhancer domains together or singly. Thus, the DNA sequence elements responsible for directing the activation of AFP transcription, its repression, and reinduction are contained in a limited segment of DNA within or 5'' to the gene (or both) and are operative in the absence of the closely linked albumin gene.