Structural organization and genomic sequence of mouse syndecan-1 gene.

Syndecan-1 is an integral membrane proteoglycan, which binds several extracellular matrix components and growth factors. Its expression follows morphogenetic rather than histological patterns during embryonic development and is regulated by epithelial-mesenchymal interactions during organogenesis. Malignant transformation has been shown to suppress syndecan-1 expression. In order to understand better the regulation of syndecan-1 expression, we have determined the structural organization of mouse syndecan-1 gene. Several genomic clones were isolated, covering the entire 23-kilobase (kb) syndecan-1 gene. All five exons, four introns, and the 5'- and 3'-flanking regions were sequenced. The first intron was very long (17,582 base pairs (bp)) if compared with the others that were only a few hundred nucleotides in length. The first exon contained only the signal sequence and exons II-IV all the glycosaminoglycan binding sites. The fifth exon resided both transmembrane and cytoplasmic domains, which are known to be conserved among the members of the syndecan family. This genomic structure explains why these members could have heterologous extracellular domains and homologous transmembrane and cytoplasmic domains. Syndecan-1 gene was shown by primer extension analysis to have three transcription initiation sites which were confirmed by polymerase chain reaction. These initiation sites were found to locate -217, -266, and -591 bp from described cDNA (Saunders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cell 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 sequence 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 polyadenylation.