Comparative genomics of regulation of heavy metal resistance in Eubacteria.
Comparative genomics of regulation of heavy metal resistance in Eubacteria.
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DOI：
10.1186/1471-2180-6-49
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发表时间：
2006-06-05
期刊：
影响因子：
4.2
通讯作者：
Gelfand MS
中科院分区：
文献类型：
--
作者：
Permina EA;Kazakov AE;Kalinina OV;Gelfand MS
真细菌中的重金属抗性（HMR）受多种系统调节，包括来自MerR家族的转录因子（COG 0789）。HMR系统的特征在于复杂的信号结构（在19或20 bp的启动子间隔区内的强回文），并且通常由转运蛋白和调节基因组成。一些HMR调节子还包括解毒系统。测序的细菌基因组的数量不断增加，尽管COG 0789型的HMR抗性调节子通常每个基因组包含很少的基因，但计算分析可能有助于理解金属解毒的细胞系统。我们研究了汞（MerR）、铜（CueR和HmrR）、镉（CadR）、铅（PbrR）和锌（ZntR）抗性系统，并证明结合蛋白质序列分析和DNA调控信号分析，可以区分COG 0789的金属依赖性成员，将对特定金属的特异性分配给未表征的基因座，并发现参与金属抗性的新基因，特别是，多铜氧化酶和铜分子伴侣，铜调节子的候选细胞色素，新的镉转运蛋白，并可能，谷胱甘肽-S-转移酶。我们的数据表明，特异性的COG 0789系统可以确定结合系统发育分析和DNA调控位点的鉴定。考虑到信号结构，我们可以充分识别使用DNA弯曲-伸直机制激活的基因。在不存在于单个基因座中的调节子成员的情况下，分析潜在的调节位点对于正确注释和预测特异性可能是至关重要的。
Heavy metal resistance (HMR) in Eubacteria is regulated by a variety of systems including transcription factors from the MerR family (COG0789). The HMR systems are characterized by the complex signal structure (strong palindrome within a 19 or 20 bp promoter spacer), and usually consist of transporter and regulator genes. Some HMR regulons also include detoxification systems. The number of sequenced bacterial genomes is constantly increasing and even though HMR resistance regulons of the COG0789 type usually consist of few genes per genome, the computational analysis may contribute to the understanding of the cellular systems of metal detoxification. We studied the mercury (MerR), copper (CueR and HmrR), cadmium (CadR), lead (PbrR), and zinc (ZntR) resistance systems and demonstrated that combining protein sequence analysis and analysis of DNA regulatory signals it was possible to distinguish metal-dependent members of COG0789, assign specificity towards particular metals to uncharacterized loci, and find new genes involved in the metal resistance, in particular, multicopper oxidase and copper chaperones, candidate cytochromes from the copper regulon, new cadmium transporters and, possibly, glutathione-S-transferases. Our data indicate that the specificity of the COG0789 systems can be determined combining phylogenetic analysis and identification of DNA regulatory sites. Taking into account signal structure, we can adequately identify genes that are activated using the DNA bending-unbending mechanism. In the case of regulon members that do not reside in single loci, analysis of potential regulatory sites could be crucial for the correct annotation and prediction of the specificity.
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