The study characterized their regulatory functions of four znt members (znt1, znt2, znt6 and znt8) in Zn homeostasis in vertebrates. We found that the −1281/−1296 bp locus on the znt1 promoter, the −1/−16 bp locus on the znt2 promoter, the −825/−839 bp locus on the znt6 promoter, the −165/−180 bp locus and the −274/−292 bp STAT3 locus on the znt8 promoter were functional MTF-1 binding sites and had metal responsive element (MRE). Zn incubation increased activities of four znt promoters, which was mediated by MRE sites on znt1, znt2, znt6 and znt8 promoters and by STAT3 binding site on znt8 promoter. Moreover, Zn activated the transcription of these znts genes through MTF-1-MRE-dependent pathway. Zn incubation up-regulated the mRNA and total protein expression of ZnT1, ZnT2 and ZnT8 at both 24 h and 48 h. Overall, for the first time, this study offered novel insights for regulatory mechanism of Zn homeostasis in vertebrates.

该研究表征了四个znt成员（ znt1 、 znt2 、 znt6和znt8 ）在脊椎动物锌稳态中的调节功能。我们发现znt1启动子上的−1281/−1296 bp基因座、 znt2启动子上的−1/−16 bp基因座、znt6启动子上的−825/−839 bp基因座、 znt6启动子上的−165/−180 bp基因座znt8启动子上的-274/-292 bp STAT3位点是功能性MTF-1结合位点，并具有金属反应元件（MRE）。 Zn孵育增加了四个znt启动子的活性，这是由znt1 、 znt2 、 znt6和znt8启动子上的MRE位点以及znt8启动子上的STAT3结合位点介导的。此外，Zn通过MTF-1-MRE依赖性途径激活这些znts基因的转录。 Zn孵育24小时和48小时均上调ZnT1、ZnT2和ZnT8的mRNA和总蛋白表达。总的来说，这项研究首次为脊椎动物锌稳态的调节机制提供了新的见解。