A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis
A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis
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DOI：
10.1093/nar/gkx762
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发表时间：
2017-11-16
影响因子：
14.9
通讯作者：
Kornfeld, Kerry
中科院分区：
文献类型：
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作者：
Dietrich, Nicholas;Schneider, Daniel L.;Kornfeld, Kerry
必需元素锌在生物学中起着至关重要的作用。高锌稳态机制开始在动物中被定义，但低锌稳态的特点很差。我们研究了秀丽隐杆线虫中的低锌稳态，因为该基因组编码14个进化保守的Zrt，Irt样蛋白（ZIP）锌转运蛋白家族成员。三个C elegans zipt基因在缺锌条件下受到调控;这些启动子含有进化上保守的基序，我们将其命名为低锌激活（LZA）元件，该元件对于响应缺锌的转录激活是必要的和充分的。这些结果表明LZA元件是低锌稳态途径的关键部分。LZA元件的转录调节需要转录因子ELT-2和介体复合物成员MDT-15。我们通过分析LZA元件在人类培养细胞中的功能来研究哺乳动物中的保守性; LZA元件介导的转录激活响应于细胞中的锌缺乏，表明低锌稳态的保守途径。我们提出，低锌稳态的途径，其中包括LZA元件和ZIP转运蛋白，平行的高锌稳态的途径，其中包括HZA元件，HIZR-1转录因子和阳离子扩散促进剂转运蛋白。
The essential element zinc plays critical roles in biology. High zinc homeostasis mechanisms are beginning to be defined in animals, but low zinc homeostasis is poorly characterized. We investigated low zinc homeostasis in Caenorhabditis elegans because the genome encodes 14 evolutionary conserved Zrt, Irt-like protein (ZIP) zinc transporter family members. Three C. elegans zipt genes were regulated in zinc-deficient conditions; these promoters contained an evolutionarily conserved motif that we named the low zinc activation (LZA) element that was both necessary and sufficient for activation of transcription in response to zinc deficiency. These results demonstrated that the LZA element is a critical part of the low zinc homeostasis pathway. Transcriptional regulation of the LZA element required the transcription factor ELT-2 and mediator complex member MDT-15. We investigated conservation in mammals by analyzing LZA element function in human cultured cells; the LZA element-mediated transcriptional activation in response to zinc deficiency in cells, suggesting a conserved pathway of low zinc homeostasis. We propose that the pathway for low zinc homeostasis, which includes the LZA element and ZIP transporters, acts in parallel to the pathway for high zinc homeostasis, which includes the HZA element, HIZR-1 transcription factor and cation diffusion facilitator transporters.