Similarities in transthyretin gene expression and differences in transcription factors: liver and yolk sac compared to choroid plexus.

The serum thyroxine-binding protein, transthyretin (TTR), is made by hepatocytes and by choroid plexus epithelium in adults and by yolk sac cells in embryogenesis. Four hepatocyte nuclear factors (HNF-1, -3, and -4 and C/EBP) that are present in liver but not in most other adult tissues bind DNA sites in the TTR gene that are sufficient to direct transgenic expression. Three of these proteins were also found in yolk sac cells, which also express the transgene. A limited transgenic construct is not active in the choroid plexus and a TTR-producing choroid plexus tumor lacks three of the liver-enriched DNA-binding proteins. We conclude that cell-specific expression of TTR is regulated at least in part by the differential cellular distribution of positive-acting transcription factors.