Genome-wide prediction of G4 DNA as regulatory motifs:: Role in Escherichia coli global regulation
Genome-wide prediction of G4 DNA as regulatory motifs:: Role in Escherichia coli global regulation
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DOI：
10.1101/gr.4508806
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发表时间：
2006-05-01
期刊：
影响因子：
7
通讯作者：
Chowdhury, S
中科院分区：
文献类型：
--
作者：
Rawal, P;Kummarasetti, VBR;Chowdhury, S
近年来，非线性DNA在复制、重组和转录中的作用已经变得明显。虽然有几项研究已经预测并表征了调控元件在序列水平上，很少有研究DNA结构作为调控基序。在这里，使用G-quadruplex或G4 DNA基序作为模型，我们研究了DNA结构在全基因组范围内转录中的作用。对18种原核生物中> 61，000个开放阅读框（ORF）的分析显示，G4基序在调控区中富集，并表明其在与转录、次级代谢物生物合成和信号转导有关的基因启动子中占优势。基于此，我们预测G4 DNA可能存在调控信号。这是支持保守的G4基序的启动子中的orthopathic基因在遗传上遥远的生物体。我们假设G4 DNA在超螺旋应激过程中的调节作用，当双链体不稳定可能导致G4形成。这与我们对大肠杆菌中55种DNA结合蛋白的靶位点分析的观察结果一致，其揭示了G4基序与全局调节因子FIS和Lrp以及σ因子RpoD（σ（70））的靶位点的显著（P < 0.001）关联。这些因子在早期生长阶段共同控制> 1000个基因，并且被认为是由超螺旋DNA诱导的。我们还预测了G4基序诱导的超螺旋敏感性为> 30操纵子在E。我们的研究结果表明G4 DNA参与了大肠杆菌中DNA拓扑结构介导的全局基因调控。杆菌
The role of nonlinear DNA in replication, recombination, and transcription has become evident in recent years. Although several studies have predicted and characterized regulatory elements at the sequence level, very few have investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4 DNA motifs as a model, we have researched the role of DNA structure in transcription on a genome-wide scale. Analyses of > 61,000 open reading frames (ORFs) across 18 prokaryotes show enrichment of G4 motifs in regulatory regions and indicate its predominance within promoters of genes pertaining to transcription, secondary metabolite biosynthesis, and signal transduction. Based on this, we predict that G4 DNA may present regulatory signals. This is supported by conserved G4 motifs in promoters of orthologous genes across phylogenetically distant organisms. We hypothesized a regulatory role of G4 DNA during supercoiling stress, when duplex destabilization may result in G4 formation. This is in line with our observations from target site analysis for 55 DNA-binding proteins in Escherichia coli, which reveals significant (P < 0.001) association of G4 motifs with target sites of global regulators FIS and Lrp and the sigma factor RpoD (sigma(70)). These factors together control > 1000 genes in the early growth phase and are believed to be induced by supercoiled DNA. We also predict G4 motif-induced supercoiling sensitivity for > 30 operons in E. coli, and our findings implicate G4 DNA in DNA-topology-mediated global gene regulation in E. coli.