Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter.
Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter.
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发表时间：
1994-12
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通讯作者：
Michael F. NasoS;Dieter R. Zimmermanng;Renato V. Iozzon
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作者：
Michael F. NasoS;Dieter R. Zimmermanng;Renato V. Iozzon
Versican 是一种模块化蛋白聚糖，参与细胞生长和分化的控制。为了了解多功能蛋白聚糖基因调控和转录控制，我们分离了跨越整个基因座的基因组克隆，包括 5'-和 3'-侧翼序列。 Versican 由 15 个外显子编码，包含超过 90 KB 对的连续 DNA。外显子组织对应于同源蛋白质编码的蛋白质子结构域，外显子大小和内含子相位具有显着的保守性。我们在糖胺聚糖结合区附近发现了一个额外的外显子，该外显子与最近鉴定的多功能蛋白聚糖的剪接变体相同（Dours-Zimmermann, M.T., and Zimmermann, D.R. (1994) J. Biol. Chem. 269, 32992-32998）。多功能蛋白聚糖启动子含有一个典型的 TATA 盒，位于转录起始位点上游约 16 个碱基对处，以及许多参与调节基因表达的转录因子的结合位点。该启动子在间充质和上皮来源的瞬时转染细胞中显示出高度功能。逐步5'删除鉴定出-209和-445碱基对之间的强增强子元件以及-445和-632碱基对之间的强负元件。这项研究为辨别多功能蛋白聚糖基因的转录控制提供了分子基础，并提供了研究与这一重要人类基因相关的遗传性疾病的机会。
Versican is a modular proteoglycan involved in the control of cellular growth and differentiation. To understand versican gene regulation and transcriptional control, we have isolated genomic clones spanning the entire gene locus including 5'- and 3'-flanking sequences. Versican was encoded by 15 exons encompassing over 90 kilobase pairs of continuous DNA. The exon organization corresponded to the protein subdomains encoded by homologous proteins, with a remarkable conservation of exon size and intron phase. We discovered an additional exon just proximal to the glycosaminoglycan-binding region that was identical to a recently identified splice variant of versican (Dours-Zimmermann, M.T., and Zimmermann, D.R. (1994) J. Biol. Chem. 269, 32992-32998). The versican promoter harbored a typical TATA box located approximately 16 base pairs upstream of the transcription start site and binding sites for a number of transcription factors involved in regulated gene expression. This promoter was shown to be highly functional in transiently transfected cells of both mesenchymal and epithelial origin. Stepwise 5' deletions identified a strong enhancer element between -209 and -445 base pairs and a strong negative element between -445 and -632 base pairs. This study provides the molecular basis for discerning the transcriptional control of the versican gene and offers the opportunity to investigate genetic disorders linked to this important human gene.