HYPOXIA-INDUCIBLE NUCLEAR FACTORS BIND TO AN ENHANCER ELEMENT LOCATED 3' TO THE HUMAN ERYTHROPOIETIN GENE
HYPOXIA-INDUCIBLE NUCLEAR FACTORS BIND TO AN ENHANCER ELEMENT LOCATED 3' TO THE HUMAN ERYTHROPOIETIN GENE
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DOI：
10.1073/pnas.88.13.5680
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发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
ANTONARAKIS, SE
中科院分区：
文献类型：
--
作者：
SEMENZA, GL;NEJFELT, MK;ANTONARAKIS, SE
人促红细胞生成素基因在肝脏和肾脏的表达受贫血或缺氧的诱导。在肝细胞核中发现了人促红细胞生成素基因的3‘端DNA酶I超敏位点。DNase I保护和凝胶迁移率改变分析表明，3‘侧翼序列有一个256碱基对的区域，可以与四个或更多不同的核因子结合，其中至少两个是由肝脏和肾脏的贫血引起的，在瞬时表达分析中，该区域起到了缺氧诱导增强子的作用。这些结果为低氧调节基因表达的分子基础提供了洞察力。
Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia.