STRUCTURAL CHARACTERIZATION OF THE COMPLETE HUMAN PERLECAN GENE AND ITS PROMOTER
STRUCTURAL CHARACTERIZATION OF THE COMPLETE HUMAN PERLECAN GENE AND ITS PROMOTER
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DOI：
10.1073/pnas.90.21.10404
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发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
IOZZO, RV
中科院分区：
文献类型：
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作者：
COHEN, IR;GRASSEL, S;IOZZO, RV
完整的内含子-外显子组织的基因编码的人串珠素（HSPG 2），主要的硫酸乙酰肝素蛋白聚糖的基底膜，已被阐明，和特定的外显子已被分配到编码序列的模块化结构域的蛋白质核心。该基因由94个外显子组成，跨越> 120 kbp的基因组DNA。外显子排列进行了分析，维斯于的模块化结构的串珠素，其中含有蛋白质结构域同源的低密度脂蛋白受体，层粘连蛋白，表皮生长因子，和神经细胞粘附分子。外显子的大小和内含子的相位是高度保守的同源基因的相应的结构域相比，这表明大多数模块化蛋白聚糖已经从一个共同的祖先进化的基因复制或外显子改组。5'侧翼区揭示了管家和生长控制相关基因的结构组织特征。它缺乏典型的TATA或CAAT盒，但它含有几个GC盒，这些盒具有转录因子SP1和ETF的结合位点。与缺乏TATA元件一致，串珠素基因含有分布在80 bp基因组DNA上的多个转录起始位点。这些结果提供了深入了解这种嵌合分子的进化，并为理解这一重要基因的转录控制提供了分子基础。
The complete intron-exon organization of the gene encoding human perlecan (HSPG2), the major heparan sulfate proteoglycan of basement membranes, has been elucidated, and specific exons have been assigned to coding sequences for the modular domains of the protein core. The gene was composed of 94 exons, spanning > 120 kbp of genomic DNA. The exon arrangement was analyzed vis-a-vis the modular structure of the perlecan, which harbors protein domains homologous to the low density lipoprotein receptor, laminin, epidermal growth factor, and neural cell adhesion molecule. The exon size and the intron phases were highly conserved when compared to the corresponding domains of the homologous genes, suggesting that most of this modular proteoglycan has evolved from a common ancestor by gene duplication or exon shuffling. The 5' flanking region revealed a structural organization characteristic of housekeeping and growth control-related genes. It lacked canonical TATA or CAAT boxes, but it contained several GC boxes with binding sites for the transcription factors SP1 and ETF. Consistent with the lack of a TATA element, the perlecan gene contained multiple transcription initiation sites distributed over 80 bp of genomic DNA. These results offer insights into the evolution of this chimeric molecule and provide the molecular basis for understanding the transcriptional control of this important gene.