Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene
Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene
复制标题
DOI：
10.1007/s002510050249
复制
发表时间：
1997-01-01
期刊：
影响因子：
3.2
通讯作者：
Krissansen, GW
中科院分区：
文献类型：
--
作者：
Leung, E;Berg, RW;Krissansen, GW
MAdCAM-1 是内皮细胞粘附分子 1，优先与白细胞 β 7 整合素 LPAM-1 (α 4 β 7) 相互作用，但也与 L-选择素以及骨髓细胞上的 VLA-4 (α 4 β 1) 相互作用，并用于引导白细胞进入粘膜和发炎组织。分离出重叠的粘粒和噬菌体 lambda 基因组克隆，揭示人类 MAdCAM-1 基因包含五个外显子，其中信号肽、两个 Ig 结构域和粘蛋白结构域各自由单独的外显子编码。跨膜结构域、胞质结构域和 3' 非翻译区在外显子 5 上一起编码。粘蛋白结构域总共包含 8 个可进行选择性剪接的重复序列。尽管不存在第三个 IgA 同源结构域的人类对应物并且缺乏粘蛋白结构域的序列保守性，但人和小鼠 MAdCAM-1 基因的基因组组织是相似的。鉴定出一种可变剪接的 MAdCAM-1 变体，它缺乏编码粘蛋白结构域的外显子 4，并且可能介导白细胞粘附到 LPAM-1，而不粘附到替代受体 L-选择素。 MAdCAM-1 基因位于 19 号染色体上的 p13.3，与 ICAM-1 和 ICAM-3 基因 (p13.2-p13.3) 非常接近。 PMA 诱导的启动子活性包含在小鼠 MAdCAM-1 基因保守的 700 个碱基对 5' 侧翼片段中，包括串联 NF-κ B 位点和 Sp1 位点。此外还有多个潜在的 AP2、Adh1 (ETF)、PEA3 和 Sp1 位点。总之，数据表明，先前报道的人类 MAdCAM-1 cDNA 确实编码小鼠 MAdCAM-1 的人类同源物，尽管 MAdCAM-1 C 端结构存在明显差异。
MAdCAM-1, the endothelial addressin cell adhesion molecule-1, interacts preferentially with the leukocyte beta 7 integrin LPAM-1 (alpha 4 beta 7), but also with L-selectin, and with VLA-4 (alpha 4 beta 1) on myeloid cells, and serves to direct leukocytes into mucosal and inflamed tissues. Overlapping cosmid and phage lambda genomic clones were isolated, revealing that the human MAdCAM-1 gene contains five exons where the signal peptide, two Ig domains, and mucin domain are each encoded by separate exons. The trans membrane domain, cytoplasmic domain, and 3' untranslated region are encoded together on exon 5. The mucin domain contains eight repeats in total that are subject to alternative splicing. Despite the absence of a human counterpart of the third IgA-homologous domain and lack of sequence conservation of the mucin domain, the genomic organizations of the human and mouse MAdCAM-1 genes are similar. An alternatively spliced MAdCAM-1 variant was identified that lacks exon 4 encoding the mucin domain, and may mediate leukocyte adhesion to LPAM-1 without adhesion to the alternate receptor, L-selectin. The MAdCAM-1 gene was located at p13.3 on chromosome 19, in close proximity to the ICAM-1 and ICAM-3 genes (p13.2-p13.3). PMA-inducible promotor activity was contained in a 700 base pair 5' flanking fragment conserved with the mouse MAdCAM-1 gene including tandem NF-kappa B sites, and an Sp1 site. and in addition multiple potential AP2, Adh1 (ETF), PEA3, and Sp1 sites. In summary, the data establish that the previously reported human MAdCAM-1 cDNA does indeed encode the human homologue of mouse MAdCAM-1, despite gross dissimilarities in the MAdCAM-1 C-terminal structures.