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首页> 外文期刊>Journal of Cellular Physiology >Divalent metal transporter 1 is a hypoxia-inducible gene.
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Divalent metal transporter 1 is a hypoxia-inducible gene.

机译：二价金属转运蛋白1是一个低氧诱导的基因。

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Our recent study revealed a high correlation between the expression of hypoxia-inducible factor-1 (HIF-1) alpha and divalent metal transporter 1 (DMT1) in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated that DMT1 might be one of the target genes of HIF-1. Here, we characterized the DMT1 exon1B promoter region and identified a functional hypoxia response element (HRE, 5'-TCAGTACCTAACGTGGCGCCACGGC-3') harboring a binding site for HIF-1. We demonstrated that hypoxia-dependent activation of a luciferase reporter gene in transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter containing the putative HRE sequence. We also showed that the HIF-1 binding site (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5'-ACGTG-3') at -327 to -323 relative to the transcription start site of the human DMT1 exon1B gene. The mutation of this sequence prevented stimulation of luciferase activity. Electrophoretic mobility shift assays revealed that the HRE sequence found in the DMT1 gene promoter was bound by HIF-1. In addition, we provide evidence that hypoxia could significantly increase ferrous uptake, while the silencing of total DMT1 by RNA interference down-regulates DMT1 expression and ferrous uptake in HepG2 cells. We conclude that DMT1 is a hypoxia-inducible gene.
机译：我们最近的研究显示高相关性在低氧诱导的表达因子- 1 (HIF-1)α和二价金属HepG2细胞转运体1 (DMT1)处理化学或物理缺氧。推测DMT1可能是其中的一个目标HIF-1的基因。exon1B启动子区域和确定了功能性缺氧反应元素(一定是,5)窝藏-TCAGTACCTAACGTGGCGCCACGGC-3HIF-1结合位点。hypoxia-dependent荧光素酶的激活记者基因转染HepG2细胞由一个片段的人类DMT1 exon1B包含假定的一定是启动子序列。还显示,HIF-1绑定网站(哈佛商学院)在DMT1 exon1B与核心启动子序列一定是(5“-ACGTG-3”)在-327年到-323年相对于转录起始站点的人类DMT1 exon1B基因。荧光素酶活动的刺激。电泳迁移率改变分析揭示这一定是DMT1中发现的基因序列子被HIF-1绑定。提供证据表明缺氧可以显著增加铁吸收,而沉默总DMT1 RNA干扰下调DMT1表达和亚铁HepG2的吸收细胞。低氧诱导的基因。

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