We conducted studies on the regulation of gene expression in placenta and liver during normal and abnormal differentiation processes. To examine expression of the human pregnancy-specific B1 glycoprotein (PSBG) gene in placenta, we isolated and characterized cDNA and genomic clones encoding this protein. PSBG shares strong sequence homology with the carcinoembryonic antigen, is a member of the immunoglobulin superfamily, and is encoded by multiple genes linked on chromosome 19. We demonstrate that the structure of the PSGG1 gene, which encodes the major PSBG transcript, PSG93, consists of 5 exons and its 3' exon contains multiple splice sites resulting in the generation of five PSBG transcripts. We also discovered that one of the PSBG genes, PSGGB, was preferentially expressed in hydatidiform molar tissues. The PSGGB-encoded species contains a deletion of one amino acid in the N protein domain as compared with the PSGG1-encoded species. Moreover, the PSGGB-encoded protein contains the Arg-Gly-Asp tripeptide which has been implicated in cellular adhesion, suggesting a possible function for these PSBG species. In our placental alkaline phosphatase (AP) project, we examined the structure-function relationship of human germ cell AP using site-directed mutagenesis and expression in COS-1 cells. Enzyme synthesis and catalytic activity of AP mutants that lack one or both of the glycosylation sites were analyzed and our data indicate that the N-linked glycans are not required for the catalytic activity or stability of germ cell AP. By site-directed mutagenesis, we demonstrate that the serine residue at position 92 is the active site of germ cell AP. In our project on liver differentiation, we examined expression of three liver genes, phosphoenolpyruvate carboxykinase (PEPCK), tyrosine aminotransferase (TAT), and albumin in a temperature-sensitive adult rat hepatocyte line. Expression of all three genes was stimulated by glucocorticoids and cAMP. However, retinoic acid enhances expression of the PEPCK gene but inhibits expression of albumin and TAT genes induced by glucocorticoids or cAMP. The PEPCK gene is mainly regulated at the transcriptional level; in contrast, the TAT gene is regulated at the post-transcriptional level.
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