Muglia L, Rothman-Denes L B
Proc Natl Acad Sci U S A. 1986 Oct;83(20):7653-7. doi: 10.1073/pnas.83.20.7653.
Albumin and alpha-fetoprotein are evolutionarily related genes that show differential and complex patterns of regulation during development. We investigated the role of the sequences flanking the transcription initiation site of the rat alpha-fetoprotein gene in transient transfection assays of hepatic and nonhepatic cell lines. Chimeric flanking regions and deletion analysis have defined the following three functionally different regions: a cell type-specific enhancer(s), encompassing 3 kilobases, located between -7 kilobase pairs and -4 kilobase pairs; a cell type-specific promoter, inactive in the absence of an enhancer and comprising at most the 180 base pairs upstream from the site of transcription initiation; and a 550-base-pair region, located between the promoter and the enhancer (at -3.5 kilobases), down-regulates transcription initiation in a cell type-specific manner and is also capable of repressing heterologous promoters. The implications of these findings with respect to the complex pattern of AFP regulation are discussed.
白蛋白和甲胎蛋白是在进化上相关的基因，在发育过程中呈现出差异且复杂的调控模式。我们在肝和非肝细胞系的瞬时转染实验中研究了大鼠甲胎蛋白基因转录起始位点侧翼序列的作用。嵌合侧翼区域和缺失分析确定了以下三个功能不同的区域：一个细胞类型特异性增强子，跨度为3千碱基，位于-7千碱基对和-4千碱基对之间；一个细胞类型特异性启动子，在没有增强子时无活性，最多包含转录起始位点上游的180个碱基对；以及一个550碱基对的区域，位于启动子和增强子之间（在-3.5千碱基处），以细胞类型特异性方式下调转录起始，并且还能够抑制异源启动子。讨论了这些发现对于甲胎蛋白复杂调控模式的意义。
