ORGANIZATION AND PROMOTER ACTIVITY OF THE MOUSE SYNDECAN-1 GENE

Syndecan-1, the prototype of a family of heparan sulfate-containing in tegral membrane proteoglycans, associates extracellularly with a varie ty of matrix molecules and growth factors and intracellularly with the actin cytoskeleton. Expressed constitutively on epithelia in mature t issues and in a developmentally regulated manner on epithelial and ind uced mesenchymal cells during embryogenesis, syndecan-1 appears to be involved in controlling the shape and organization of cells and tissue s. To better understand the function and regulation of syndecan- 1, we determined the structure of the mouse syndecan-1 gene (Synd-1). Synd- 1 is approximately 19.5 kilobases in size and is organized into five e xons that appear conserved in other family members. Exon 1 encodes the signal peptide; exon 2, the N-terminal glycosaminoglycan attachment r egion; exon 3, the bulk of the extracellular domain; exon 4, the prote ase-susceptible site; and exon 5, the transmembrane and cytoplasmic do mains which are highly homologous between syndecan family members. Syn d-1 has three transcriptional start sites, two polyadenylation sites, and is not alternatively spliced to produce its 2.6- and 3.4-kilobase mRNA species. Upstream sequences have promoter activity and contain TA TA and CAAT boxes as well as a variety of other potential binding site s for transcription factors, including Sp1 (GC box), NF-kappaB, MyoD ( E box), and Antennapedia. The structure of the promoter region suggest s that control of Synd-1 expression is both constitutive and developme ntally regulated. Because Synd-1 exons encode discrete functional doma ins of the syndecan-1 protein that are conserved throughout the syndec an family, all syndecan genes are likely derived from a common ancesto r.