Multiple signaling systems target a core set of transition metal homeostasis genes using similar binding motifs
Multiple signaling systems target a core set of transition metal homeostasis genes using similar binding motifs
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DOI：
10.1111/mmi.13909
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发表时间：
2018-03-01
影响因子：
3.6
通讯作者：
Mukhopadhyay, Aindrila
中科院分区：
文献类型：
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作者：
Garber, Megan E.;Rajeev, Lara;Mukhopadhyay, Aindrila
细菌对金属的反应需要复杂的调节。我们报道了反硝化细菌stutzeri假单胞菌RCH2中铜和锌抗性基因被三个双组分调控蛋白CopR1， CopR2和CzcR重叠调控。我们进行了全基因组评估，以确定两个相似的调控因子CopR1和CopR2的基因靶标，并将结果与CzcR的基因靶标进行了比较，CzcR与锌信号有关。我们发现CopRs和CzcR在很大程度上具有共同的靶点，并且交叉调控一组核心的stutzeri铜和锌反应基因。我们确定这种交叉调控是由靶基因上游调控区域的保守结合基序实现的。交叉调节是生理学上相关的，因为这些调节剂协同和拮抗多铜氧化酶，金属外排和隔离系统。CopR1和CopR2上调了两个编码铜耐受基因的cop操纵子，而这三个调控子都下调了一个假定的铜伴侣蛋白Psest_1595。CzcR也上调了oprD基因和CzcIABC Zn2+外排系统，而CopR1和CopR2下调了这些基因。我们的研究表明，铜和锌的交叉调控可能是有利的，在P. stutzeri中，这是通过多个反应调节因子的共享结合基序实现的。
Bacterial response to metals can require complex regulation. We report an overlapping regulation for copper and zinc resistance genes in the denitrifying bacterium, Pseudomonas stutzeri RCH2, by three two-component regulatory proteins CopR1, CopR2 and CzcR. We conducted genome-wide evaluations to identify gene targets of two paralogous regulators, CopR1 and CopR2, annotated for copper signaling, and compared the results with the gene targets for CzcR, implicated in zinc signaling. We discovered that the CopRs and CzcR have largely common targets, and crossregulate a core set of P. stutzeri copper and zinc responsive genes. We established that this crossregulation is enabled by a conserved binding motif in the upstream regulatory regions of the target genes. The crossregulation is physiologically relevant as these regulators synergistically and antagonistically target multicopper oxidases, metal efflux and sequestration systems. CopR1 and CopR2 upregulate two cop operons encoding copper tolerance genes, while all three regulators downregulate a putative copper chaperone, Psest_1595. CzcR also upregulated the oprD gene and the CzcIABC Zn2+ efflux system, while CopR1 and CopR2 downregulated these genes. Our study suggests that crossregulation of copper and zinc homeostasis can be advantageous, and in P. stutzeri this is enabled by shared binding motifs for multiple response regulators.