Vezf1/DB1 is an endothelial cell-specific transcription factor that regulates expression of the endothelia-1 promoter
Vezf1/DB1 is an endothelial cell-specific transcription factor that regulates expression of the endothelia-1 promoter
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DOI：
10.1074/jbc.m105166200
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发表时间：
2001-10-19
影响因子：
4.8
通讯作者：
Patterson, C
中科院分区：
文献类型：
--
作者：
Aitsebaomo, J;Kingsley-Kallesen, ML;Patterson, C
血管内皮内的协调基因调控是发育过程中正常心血管模式和成年期血管稳态所必需的，但对调节内皮转录事件的机制知之甚少。血管内皮锌指1 (Vezf1)/DB1是最近发现的一种含锌指蛋白，在内皮细胞发育过程中特异性表达。在本报告中，我们证明了Vezf1/ DB1是一种核定位蛋白，在瞬时转染试验中，以不依赖于税的方式，有效地特异性激活由人内皮素-1启动子介导的转录。利用缺失诱变和电泳迁移率转移的组合分析，一个新的Vezf1/ db1响应元件定位于一个6碱基对（bp）基序ACCCCC，位于内皮素-1转录起始位点上游47个位置。重组Vezf1/DB1也与该序列结合，并且该元件的2-by突变消除了内皮素-1启动子对Vezf1/DB1的响应性。Vezf1/DB1可以通过内皮细胞核复合物中与该元件结合的特异性抗体进行鉴定。Vezf1/DB1对内皮素-1启动子活性的调控为内皮素-1在发育过程中的表达和维持血管张力提供了机制；Vezf1/DB1本身是修饰内皮细胞表型的候选转录因子，以适当地组装和维持心血管系统。
Coordinated gene regulation within the vascular endothelium is required for normal cardiovascular patterning during development and for vascular homeostasis during adulthood, yet little is known about the mechanisms that regulate endothelial transcriptional events. Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/ DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Using a combination of deletion mutagenesis and electrophoretic mobility shift assays, a novel Vezf1/DB1-responsive element was localized to a 6-base pair (bp) motif, ACCCCC, located 47 by upstream of the endothelin-1 transcription start site. Recombinant Vezf1/DB1 also bound to this sequence, and a 2-by mutation in this element abolished Vezf1/DB1 responsiveness by the endothelin-1 promoter. Vezf1/DB1 could be identified with a specific antibody in nuclear complexes from endothelial cells that bound to this element. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone; Vezf1/DB1 itself is a candidate transcription factor for modifying endothelial cell phenotypes in order to appropriately assemble and maintain the cardiovascular system.