Cybulsky M I, Fries J W, Williams A J, Sultan P, Eddy R, Byers M, Shows T, Gimbrone M A, Collins T
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7859-63. doi: 10.1073/pnas.88.17.7859.
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 approximately 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.
血管细胞黏附分子1（VCAM-1）是一种细胞表面糖蛋白，可黏附某些血液白细胞和肿瘤细胞，在包括动脉粥样硬化在内的多种病理状况下，由活化的内皮细胞表达。编码VCAM1基因的基因组克隆已被分离，并确定了该基因的结构。该基因在人类基因组中以单拷贝形式存在，包含9个外显子，跨越约25千碱基对的DNA。外显子2 - 8包含C2或H型免疫球蛋白结构域。由于选择性mRNA剪接事件，包括包含或排除外显子5，人类基因可产生至少两种不同的VCAM-1前体。一个共有TATAA元件位于转录起始位点上游。VCAM1启动子包含NF-κB、转录因子GATA家族的共有结合位点以及一个AP1位点。基于对人 - 鼠杂交细胞系的分析和原位杂交，VCAM1基因被定位到染色体1的1p31 - 32区域。人类VCAM1基因的结构分析为选择性mRNA剪接提供了基础，并为阐明VCAM-1表达的调控提供了初步方法。
