Hypoxia regulatory elements of the human vascular endothelial growth factor gene.
Hypoxia regulatory elements of the human vascular endothelial growth factor gene.
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发表时间：
1994
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通讯作者：
Alexander G. Minchenko;S. Salceda;T. L. Bauer;Jose F. Caro
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作者：
Alexander G. Minchenko;S. Salceda;T. L. Bauer;Jose F. Caro
血管内皮生长因子（VEGF）的表达是高度刺激缺氧，在体外和体内。最近的研究结果表明，VEGF基因利用与促红细胞生成素基因相似的氧感应机制。然而，控制VEGF对缺氧反应的基因组序列在很大程度上是未知的。在利用HeLa细胞中的瞬时转染测定中，我们确定了低氧/钴应答增强子元件存在于人VEGF基因的5'和3'侧翼区。3'增强子包含在位于多聚腺苷酸化位点下游约60 bp的160 bp片段中。它含有一段约12 bp的序列，与促红细胞生成素缺氧反应增强子中的序列高度同源。5'侧翼增强子包含在位于起始位点上游约800 bp的100 bp片段中。该片段不包含与促红细胞生成素增强子的显著同源性。因此，似乎VEGF基因对缺氧的反应由两个调控元件控制;一个可能与促红细胞生成素增强子相关，另一个似乎是完全无关的序列。
Vascular endothelial growth factor (VEGF) expression is highly stimulated by hypoxia, both in vitro and in vivo. Recent findings suggest that the VEGF gene utilizes an oxygen sensing mechanism similar to the one used by the erythropoietin gene. The genomic sequences that control the VEGF response to hypoxia are, however, largely unknown. In utilizing transient transfection assays in HeLa cells we determined that hypoxia/cobalt responsive enhancer elements are present at the 5' and 3' flanking regions of the human VEGF gene. The 3' enhancer is contained in a 160 bp fragment located about 60 bp downstream of the polyadenylation site. It contains a sequence stretch of about 12 bp which are highly homologous to sequences in the erythropoietin hypoxia-responsive enhancer. The 5' flanking enhancer is contained in a 100 bp fragment located about 800 bp upstream of the start site. This fragment does not contain significant homologies with the erythropoietin enhancer. Thus, it appears that the response to hypoxia of the VEGF gene is controlled by two regulatory elements; one which may be related to the erythropoietin enhancer and a second, which appears to be a completely unrelated sequence.