Postnatal repression of the alpha-fetoprotein gene is enhancer independent

The mammalian liver undergoes a number of dramatic changes in gene expression during development. One of these is typified by the alpha-fetoprotein (AFP) gene, which is activated in the fetal liver but undergoes a transcriptional decline at birth. In contrast, although activated at the same time during fetal development, albumin gene transcription is maintained at high levels in adult animals. To determine whether the postnatal decline in AFP gene transcription is mediated through its distal enhancers or through more proximal elements surrounding the promoter or structural gene, chimeric genes bearing substitutions of albumin gene cis-acting elements for the equivalent AFP gene elements were introduced into the germ line of mice. The expression of the transgenes was then analyzed at various stages of development. Our results indicate that the AFP gene enhancers are not involved in the postnatal decline in AFP transcription. Rather, a region within the first kilobase of DNA upstream of the AFP gene, including its promoter, and/or portions of the structural gene is sufficient to direct postnatal repression of the gene.