Hammer R E, Krumlauf R, Camper S A, Brinster R L, Tilghman S M
Science. 1987 Jan 2;235(4784):53-8. doi: 10.1126/science.2432657.
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.
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上游调控元件，这些元件表现为典型的增强子。现在发现，当通过将克隆的DNA片段显微注射到受精卵中而引入小鼠基因组时，这些增强子中至少有一个是AFP基因组织特异性表达所必需的。每个增强子都能在适当的组织中指导表达，即卵黄囊的脏内胚层、胎儿肝脏和胃肠道，但每个增强子在这三种组织中发挥的影响不同。这些差异可能解释了AFP基因表达水平的组织特异性多样性。当引入的基因与增强子结构域一起或单独连接时，它会模拟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。因此，负责指导AFP转录激活、抑制和再诱导的DNA序列元件包含在基因内部或5'端（或两者）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也能发挥作用。
