Transcriptional Responses of Copper-Transport-Related Genes ctr1, ctr2 and atox1 and Their Roles in the Regulation of Cu Homeostasis in Yellow Catfish Pelteobagrus fulvidraco.
Transcriptional Responses of Copper-Transport-Related Genes ctr1, ctr2 and atox1 and Their Roles in the Regulation of Cu Homeostasis in Yellow Catfish Pelteobagrus fulvidraco.
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DOI：
10.3390/ijms232012243
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发表时间：
2022-10-13
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在这里，我们研究了CTR1、CTR2和ATOX1启动子在亚洲国家常见的淡水硬骨鱼黄斑叉尾鱼中的功能。我们获得了CTR1、CTR2和ATOX1启动子的1359bp、1842bp和1825bp的序列，并预测了它们启动子上的关键转录因子结合位点，包括MRE、SREBP1、NRF2、KLF4和STAT3。铜对不同地区的CTR1、CTR2和ATOX1启动子活性的影响不同。我们发现ATOX1启动子中的−326/−334BP和−1232/−1240BP是功能上的NRF2结合位点，负调控ATOX1启动子的活性。CTR1启动子上的−91/−100bP和ATOX1启动子上的−2 32/−2 41bP和−699/−708bP是SREBP1的功能结合位点，它们正向控制CTR1和ATOX1启动子的活性。铜抑制NRF2与atox1启动子的结合能力，但促进SREBP1与CTR1和atox1启动子的结合能力。与适量饲料铜组相比，饲料中过量铜显著下调了肝脏CTR1、CTR2和ATOX1的mRNA和总蛋白的表达。亚细胞定位显示，CTR1主要定位于细胞膜，CTR2主要定位于细胞膜和溶酶体，ATOX1主要定位于细胞质。综上所述，我们在转录水平上论证了三种铜转运蛋白的调控机制，并在CTR1、CTR2和ATOX1启动子中发现了具有功能的NRF2和SREBP1反应元件，这为研究它们在鱼类铜稳态调控中的作用提供了新的思路。
Here, we characterized the function of ctr1, ctr2 and atox1 promoters in yellow catfish Pelteobagrus fulvidraco, a common freshwater teleost in Asian countries. We obtained 1359 bp, 1842 bp and 1825 bp sequences of ctr1, ctr2 and atox1 promoters, and predicted key transcription factor binding sites on their promoters, including MRE, SREBP1, NRF2, KLF4 and STAT3. Cu differentially influenced the activities of ctr1, ctr2 and atox1 promoters from different regions. We found that the −326/−334 bp and −1232/−1240 bp locus in the atox1 promoter were functional NRF2 binding sites, which negatively controlled the activity of the atox1 promoter. The −91/−100 bp locus in the ctr1 promoter and −232/−241 bp and −699/−708 bp locus in the atox1 promoter were functional SREBP1 binding sites, which positively controlled the activities of ctr1 and atox1 promoters. Cu inhibited the NRF2 binding ability to the atox1 promoter, but promoted the SREBP1 binding ability to the ctr1 and atox1 promoters. Dietary Cu excess significantly down-regulated hepatic mRNA and total protein expression of CTR1, CTR2 and ATOX1 of yellow catfish, compared to the adequate dietary Cu group. The subcellular localization showed that CTR1 was mainly localized on the cell membrane, CTR2 in the cell membrane and the lysosome, and ATOX1 in the cytoplasm. In conclusion, we demonstrated the regulatory mechanism of three Cu transporters at the transcription levels, and found the functional NRF2 and SREBP1 response elements in ctr1, ctr2 and atox1 promoters, which provided new insights into their roles in the regulation of Cu homeostasis in fish.
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影响因子：
9.2
作者：
Gong G;Dan C;Xiao S;Guo W;Huang P;Xiong Y;Wu J;He Y;Zhang J;Li X;Chen N;Gui JF;Mei J
通讯作者：
Mei J
影响因子：
3
作者：
McRae, Reagan;Lai, Barry;Fahrni, Christoph J.
通讯作者：
Fahrni, Christoph J.
DOI：
10.1016/j.bbamcr.2012.02.011
发表时间：
2012-09
影响因子：
5.1
作者：
Nevitt, Tracy;Oehrvik, Helena;Thiele, Dennis J.
通讯作者：
Thiele, Dennis J.
影响因子：
5.6
作者：
Zhuo MQ;Luo Z;Xu YH;Li DD;Pan YX;Wu K
通讯作者：
Wu K
影响因子：
5.9
作者：
Pang Y;Xu X;Xiang X;Li Y;Zhao Z;Li J;Gao S;Liu Q;Mai K;Ai Q
通讯作者：
Ai Q