STRUCTURAL ORGANIZATION AND GENOMIC SEQUENCE OF MOUSE SYNDECAN-1 GENE

Syndecan-1 is an integral membrane proteoglycan, which binds several e xtracellular matrix components and growth factors. Its expression foll ows morphogenetic rather than histological patterns during embryonic d evelopment and is regulated by epithelial-mesenchymal interactions dur ing organogenesis. Malignant transformation has been shown to suppress syndecan-1 expression. In order to understand better the regulation o f syndecan-1 expression, we have determined the structural organizatio n of mouse syndecan-1 gene. Several genomic clones were isolated, cove ring the entire 23-kilobase (kb) syndecan-1 gene. All five exons, four introns, and the 5'- and 3'-flanking regions were sequenced. The firs t intron was very long (17,582 base pairs (bp)) if compared with the o thers that were only a few hundred nucleotides in length. The first ex on contained only the signal sequence and exons II-IV all the glycosam inoglycan binding sites. The fifth exon resided both transmembrane and cytoplasmic domains, which are known to be conserved among the member s of the syndecan family. This genomic structure explains why these me mbers could have heterologous extracellular domains and homologous tra nsmembrane and cytoplasmic domains. Syndecan-1 gene was shown by prime r extension analysis to have three transcription initiation sites whic h were confirmed by polymerase chain reaction. These initiation sites were found to locate -217, -266, and -591 bp from described cDNA (Saun ders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cel l Biol. 108, 1547-1556). Within the 5'-end of the gene a 2000-bp-long CpG nucleotide-rich sequence resembling a CpG island was found, which started from the transcription initiation sites and ended in the first intron. At the 3'-end of the gene an other polyadenylation signal seq uence was revealed 638 bp downstream from the first one. The two mRNAs (2.6 kb and 3.4 kb) were shown to be produced by alternative polyaden ylation.