CHARACTERIZATION AND TRANSCRIPTIONAL ACTIVITY OF THE MOUSE BILIARY-GLYCOPROTEIN-1-GENE, A CARCINOEMBRYONIC ANTIGEN-RELATED GENE

The mouse biliary glycoprotein 1 gene (bgp1) encodes several multifunc tional glycoprotein isoforms. These glycoproteins represent members of the carcinoembryonic antigen (CEA) family which belongs to the immuno globulin superfamily. The Bgp1 glycoproteins function as cell adhesion molecules and receptors for the mouse hepatitis viruses. In contrast to CEA, whose overexpression has been correlated with cancer progressi on, the human and mouse Bgp proteins are generally down-regulated upon tumor formation. In this study, we report on the mouse bgp1 gene orga nization and transcriptional activation. We have isolated phage and co smid clones encompassing the entire bgp1 coding region. This gene cons ists of nine exons, some of which are subjected to alternative splicin g producing a minimum of four splice variants. A comparison of the mur ine bgp1 proximal promoter with the human BGP and mouse cea10/bgp3 gen es revealed sequence conservation of 66% and 95%, respectively. RNase protection assays and primer extension analyses indicated that the mou se bgp1 transcriptional start site is positioned 240 nucleotides upstr eam of the ATG translational initiation codon, which is 140 nucleotide s further upstream than in any other CEA family member. The bgp1 promo ter is transcriptionally active in reporter gene activation in vitro t ransfection studies and in vivo using a bgp1-containing cosmid clone. We identified three putative AP-2 or AP-2-like sites and an upstream s timulatory factor (USF) recognition sequence within the proximal mouse bgp1 promoter region at positions similar to those used by the human BGP promoter region. These data suggest that the regulation of the mou se and human BGP genes may follow some common spatial and temporal exp ression. Interestingly, the bgp1 proximal promoter and coding region a re also well conserved throughout evolution.