GENE STRUCTURE, CHROMOSOMAL LOCATION, AND BASIS FOR ALTERNATIVE MESSENGER-RNA SPLICING OF THE HUMAN VCAM1 GENE
GENE STRUCTURE, CHROMOSOMAL LOCATION, AND BASIS FOR ALTERNATIVE MESSENGER-RNA SPLICING OF THE HUMAN VCAM1 GENE
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DOI：
10.1073/pnas.88.17.7859
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发表时间：
1991-09-01
影响因子：
11.1
通讯作者：
COLLINS, T
中科院分区：
文献类型：
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作者：
CYBULSKY, MI;FRIES, JWU;COLLINS, T
血管细胞粘附分子1（VCAM-1）是一种粘附于某些血液白细胞和肿瘤细胞的细胞表面糖蛋白，在包括动脉粥样硬化在内的多种病理状态下由活化的内皮细胞表达。分离编码VCAM 1基因的基因组克隆，并确定该基因的组织。该基因以单拷贝存在于人类基因组中，包含9个外显子，跨越几乎等于25个DNA酶。外显子2-8含有C2或H型免疫球蛋白结构域。作为包括或排除外显子5的选择性mRNA剪接事件的结果，可以从人基因产生至少两种不同的VCAM-1前体。共有TATAA元件位于转录起始位点的上游。VCAM 1启动子包含NF-κ-B、转录因子的加塔家族的共有结合位点以及AP 1位点。通过对人-鼠杂交细胞系和原位杂交分析，将VCAM 1基因定位于1号染色体1 p31 -32区域。人VCAM 1基因的结构分析提供了选择性mRNA剪接的基础和阐明VCAM-1表达调控的初步方法。
Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein adhesive for certain blood leukocytes and tumor cells, which is expressed by activated endothelium in a variety of pathologic conditions including atherosclerosis. Genomic clones encoding the VCAM1 gene were isolated and the organization of the gene was determined. The gene, which is present in a single copy in the human genome, contains 9 exons spanning almost-equal-to 25 kilobases of DNA. Exons 2-8 contain C2 or H-type immunoglobulin domains. At least two different VCAM-1 precursors can be generated from the human gene as a result of alternative mRNA splicing events, which include or exclude exon 5. A consensus TATAA element is located upstream of the transcriptional start site. The VCAM1 promoter contains consensus binding sites for NF-kappa-B, the GATA family of transcription factors, as well as an AP1 site. The VCAM1 gene was assigned to the 1p31-32 region of chromosome 1 based on the analysis of human-mouse hybrid cell lines and in situ hybridization. Structural analysis of the human VCAM1 gene provides the basis for alternative mRNA splicing and an initial approach to elucidating the regulation of VCAM-1 expression.