Functional analysis of MTF-1 and MT promoters and their transcriptional response to zinc (Zn) and copper (Cu) in yellow catfish Pelteobagrus fulvidraco
Functional analysis of MTF-1 and MT promoters and their transcriptional response to zinc (Zn) and copper (Cu) in yellow catfish Pelteobagrus fulvidraco
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黄颡鱼MTF-1和MT启动子的功能分析及其对锌（Zn）和铜（Cu）的转录响应
DOI：
10.1016/j.chemosphere.2019.125792
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发表时间：
2020-05-01
期刊：
影响因子：
8.8
通讯作者：
Luo, Zhi
中科院分区：
文献类型：
--
作者：
Chen, Guang-Hui;Lv, Wuhong;Luo, Zhi
金属应答转录因子-1（MTF-1）和金属硫蛋白（MT）的表达参与金属稳态和解毒。本研究对黄颡鱼mV-1和mt基因启动子的结构和功能进行了研究。在转录因子的启动子区域预测了许多重要的结合位点，如热休克启动子元件（HSE）和金属响应元件（MRE）。铜对mtf-1启动子活性无显著影响，锌可提高mtf-1启动子活性。铜和锌诱导mt启动子活性的增加。mtf-1启动子的HSE位点是锌诱导mtf-1转录激活的功能结合位点。Zn和Cu通过MTF-1和MRE依赖的途径诱导mt基因的转录激活。以黄颡鱼原代肝细胞为研究对象，发现Cu和Zn可诱导MT的表达; Cu对MTF-1的mRNA和总蛋白水平无显著影响，而Zn可上调其mRNA和总蛋白的表达。Zn和Cu处理也上调了MTF-1核蛋白的表达，这反过来又增加了mt的表达。综上所述，这些结果揭示了MT和MTF-1在Zn或Cu处理下的转录调控，并为脊椎动物Cu和Zn稳态的调节提供了一些机制。(C)2020爱思唯尔有限公司版权所有。
Metal-responsive transcription factor-1 (MTF-1) and metallothionein (MT) expression are involved in metal homeostasis and detoxification. Here, we characterized the structure and functions of mV-1 and mt promoters in yellow catfish Pelteobagrus fulvidraco. Many important binding sites of transcriptional factors, such as heat shock promoter element (HSE) and metal responsive element (MRE), were predicted on their promoter regions. Cu did not significantly influence the activity of mtf-1 promoter, but Zn increased its promoter activity. Cu and Zn induced the increase of mt promoter activity. HSE site of mtf-1 promoter was the functional binding locus responsible for Zn-induced mtf-1 transcriptional activation. Zn and Cu induced transcriptional activation of mt gene through the MTF-1- and MRE-dependent pathway. Using primary hepatocytes of yellow catfish, we found that Cu and Zn induced the mt expression; Cu did not significantly influence the mRNA and total protein levels of MTF-1, but Zn up-regulated its mRNA and total protein expression. Both Zn and Cu treatment also up-regulated MTF-1 nuclear protein expression, which in turn increased the mt expression. Taken together, these findings delineated the transcriptional regulation of MT and MTF-1 under Zn or Cu treatments, and provided some mechanisms for the regulation of Cu and Zn homeostasis in vertebrates. (C) 2020 Elsevier Ltd. All rights reserved.