Cell type-specific negative regulatory element in the control region of the rat alpha-fetoprotein gene

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.