Vihinen T, Auvinen P, Alanen-Kurki L, Jalkanen M
Department of Medical Biochemistry, University of Turku, Finland.
J Biol Chem. 1993 Aug 15;268(23):17261-9.
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.
Syndecan-1是一种整合膜蛋白聚糖，它能结合多种细胞外基质成分和生长因子。在胚胎发育过程中，其表达遵循形态发生模式而非组织学模式，并在器官发生过程中受上皮-间充质相互作用的调控。恶性转化已被证明会抑制Syndecan-1的表达。为了更好地理解Syndecan-1表达的调控机制，我们确定了小鼠Syndecan-1基因的结构组织。分离出了几个基因组克隆，覆盖了整个23千碱基（kb）的Syndecan-1基因。对所有五个外显子、四个内含子以及5'和3'侧翼区域进行了测序。与其他长度仅为几百个核苷酸的内含子相比，第一个内含子非常长（17582个碱基对（bp））。第一个外显子仅包含信号序列，外显子II-IV包含所有糖胺聚糖结合位点。第五个外显子包含跨膜和细胞质结构域，已知这些结构域在Syndecan家族成员中是保守的。这种基因组结构解释了为什么这些成员可能具有异源的细胞外结构域以及同源的跨膜和细胞质结构域。通过引物延伸分析表明Syndecan-1基因有三个转录起始位点，这一点通过聚合酶链反应得到了证实。这些起始位点位于距所述cDNA（桑德斯，S.，亚尔卡宁，M.，奥法雷尔，S.，和伯恩菲尔德，M.（1989年）《细胞生物学杂志》108，1547 - 1556）-217、-266和-591 bp处。在基因的5'端发现了一个2000 bp长的富含CpG核苷酸的序列，类似于一个CpG岛，它从转录起始位点开始，在第一个内含子中结束。在基因的3'端，在第一个聚腺苷酸化信号序列下游638 bp处发现了另一个聚腺苷酸化信号序列。这两种mRNA（2.6 kb和3.4 kb）被证明是通过可变聚腺苷酸化产生的。
