Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in bacteria: radioresistance of D. radiodurans involves G4 DNA-mediated regulation.
Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in bacteria: radioresistance of D. radiodurans involves G4 DNA-mediated regulation.
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DOI：
10.1093/nar/gks1071
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发表时间：
2013-01-07
影响因子：
14.9
通讯作者：
Chowdhury S
中科院分区：
文献类型：
--
作者：
Beaume N;Pathak R;Yadav VK;Kota S;Misra HS;Gautam HK;Chowdhury S
在基因启动子中发现了大量富含鸟嘌呤的序列，这些序列具有采用称为G-四链体（或G4 DNA）的非规范二级结构的潜力。尽管越来越多的兴趣，四链体DNA基序在内在细胞功能的调节作用仍然知之甚少。在此，我们询问启动子中潜在的G4（PG 4）DNA的出现是否与细菌中的特定功能相关。使用标准化的启动子-PG 4-含量（PG 4 P）指数，我们分析了19个良好注释的物种中的>60 000个启动子，用于（a）功能类（es）和（B）富含PG 4 P的基因。出乎意料的是，PG 4相关的功能类是生物体特异性的，这表明PG 4基序可能赋予生物体特异性功能。作为一个案例研究，我们分析了辐射抗性。有趣的是，使用PG 4P的21个基因的无监督聚类，对辐射抗性至关重要，将包括耐辐射异常球菌在内的三种耐辐射微生物分组。基于这些预测，我们测试并发现，在纳摩尔量的细胞内四链体结合配体N-甲基中卟啉（NMM）的存在下，D。抗辐射药物的衰减率为60%。此外，RecF重组修复途径的重要组分recA、recF、recO、recR和recQ基因被发现含有启动子-PG 4基序，并且在NMM存在下也被下调。总之，这些结果提供了第一个证据表明，辐射抗性可能涉及G4 DNA介导的调节和支持的基本原理，启动子PG 4影响选择性功能。
A remarkable number of guanine-rich sequences with potential to adopt non-canonical secondary structures called G-quadruplexes (or G4 DNA) are found within gene promoters. Despite growing interest, regulatory role of quadruplex DNA motifs in intrinsic cellular function remains poorly understood. Herein, we asked whether occurrence of potential G4 (PG4) DNA in promoters is associated with specific function(s) in bacteria. Using a normalized promoter-PG4-content (PG4P) index we analysed >60 000 promoters in 19 well-annotated species for (a) function class(es) and (b) gene(s) with enriched PG4P. Unexpectedly, PG4-associated functional classes were organism specific, suggesting that PG4 motifs may impart specific function to organisms. As a case study, we analysed radioresistance. Interestingly, unsupervised clustering using PG4P of 21 genes, crucial for radioresistance, grouped three radioresistant microorganisms including Deinococcus radiodurans. Based on these predictions we tested and found that in presence of nanomolar amounts of the intracellular quadruplex-binding ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was attenuated by ∼60%. In addition, important components of the RecF recombinational repair pathway recA, recF, recO, recR and recQ genes were found to harbour promoter-PG4 motifs and were also down-regulated in presence of NMM. Together these results provide first evidence that radioresistance may involve G4 DNA-mediated regulation and support the rationale that promoter-PG4s influence selective functions.
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影响因子：
14.9
作者：
Baral A;Kumar P;Halder R;Mani P;Yadav VK;Singh A;Das SK;Chowdhury S
通讯作者：
Chowdhury S
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作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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