The distal location of the iron responsive region of the hepcidin promoter.
The distal location of the iron responsive region of the hepcidin promoter.
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DOI：
10.1182/blood-2007-05-091108
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发表时间：
2007-11
期刊：
影响因子：
20.3
通讯作者：
J. Truksa;Pauline L. Lee;Hongfan Peng;Jonathan M. Flanagan;E. Beutler
中科院分区：
文献类型：
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作者：
J. Truksa;Pauline L. Lee;Hongfan Peng;Jonathan M. Flanagan;E. Beutler
铁调素转录对铁的反应在活体小鼠中已被反复记录，但很难在离体系统中证明这种反应。我们已经用质粒构建体流体动力学转染小鼠，所述质粒构建体由鼠铁调素1启动子和与萤火虫荧光素酶报告基因融合的启动子片段组成。该方法使我们能够定量铁调素启动子对维持缺铁饮食的小鼠短期喂食高铁饮食的反应。我们发现，从翻译开始的上游1.6 Kb和1.8 Kb之间的启动子区域是必不可少的响应铁。-260 bp ~-1.6 Kb之间的启动子区域对铁调素启动子的铁响应性不是必需的。我们绘制的铁反应区域与HepG 2细胞对骨形态发生蛋白刺激的体外反应所需的区域相同，并且不同于LPS/IL-6反应区域。
The response of hepcidin transcription to iron has been repeatedly documented in living mice, but it is difficult to demonstrate the response in ex vivo systems. We have hydrodynamically transfected mice with plasmid constructs composed of a murine hepcidin 1 promoter and fragments of the promoter fused to a firefly luciferase reporter. This method enabled us to quantitate the response of the hepcidin promoter to short-term feeding of a high-iron diet to mice that have been maintained on an iron-deficient diet. We show that the region of the promoter between 1.6 Kb and 1.8 Kb upstream from the start of translation is essential for the response to iron. The promoter region between -260 bp and -1.6 Kb is not essential for the iron responsiveness of hepcidin promoter. The iron-responsive region that we have mapped is the same region required for the in vitro response of HepG2 cells to stimulation with bone morphogenetic proteins and differs from the LPS/IL-6 responsive area.