Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells
Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells
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DOI：
10.1101/gad.11.1.72
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发表时间：
1997-01-01
影响因子：
10.5
通讯作者：
Russell, DW
中科院分区：
文献类型：
--
作者：
Tian, H;McKnight, SL;Russell, DW
在这里，我们描述的PAS结构域转录因子称为内皮PAS-1（EPAS 1）的克隆和表征。该蛋白与缺氧诱导因子（HIE-1 α）具有48%的序列同一性，与基本螺旋-环-螺旋/PAS结构域转录因子家族的其他成员具有较小的相似性。与HIE-1 α一样，EPAS 1结合并激活最初从促红细胞生成素基因分离并含有序列5 ′-GCCCTACGTGCTGTCTCA-3 ′的DNA元件的转录。低氧条件刺激HIF-1 α和EPAS 1的激活。在靶基因的转录激活之前，EPAS 1与芳烃核转运蛋白形成异二聚体复合物。EPAS 1表达仅限于小鼠胚胎的内皮，并且与其细胞类型特异性表达模式一致，能够特异性激活内皮酪氨酸激酶基因Tie-2的转录。这些观察结果提出了这样的可能性，即EPAS 1可能代表血管形成的重要调节因子，可能涉及响应缺氧的内皮细胞基因表达的调节。
Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1). This protein shares 48% sequence identity with hypoxia inducible factor (HIE-1 alpha) and lesser similarity with other members of the basic helix-loop-helix/PAS domain family of transcription factors. Like HIE-1 alpha, EPAS1 binds to and activates transcription from a DNA element originally isolated from the erythropoietin gene and containing the sequence 5'-GCCCTACGTGCTGTCTCA-3'. Activation by both HIF-1 alpha and EPAS1 is stimulated by hypoxic conditions. EPAS1 forms a heterodimeric complex with the aryl hydrocarbon nuclear transporter prior to transcriptional activation of target genes. EPAS1 expression is limited to the endothelium of mouse embryos and, in agreement with its cell type-specific expression pattern, is capable of specifically activating the transcription of the endothelial tyrosine kinase gene Tie-2. These observations raise the possibility that EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia.