Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription
Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription
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DOI：
10.1101/gr.6905408
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发表时间：
2008-02-01
期刊：
影响因子：
7
通讯作者：
Li, Ning
中科院分区：
文献类型：
--
作者：
Du, Zhuo;Zhao, Yiqiang;Li, Ning
G-四链体或G4 DNA，在富含G的序列中形成的四链DNA结构，已被假设为参与基因调控的结构基序。在这项研究中，我们研究了潜在的G4 DNA基序（PG4Ms）位于整个人类基因组的基因的假定的转录调控区（TRR，-500到+500）的调节作用。我们发现，PG4Ms在500 bp的区域下游的注释转录起始位点（TSS; PG4M（D500））与基因表达。一般来说，PG4M（D500）阳性基因的表达水平高于PG4MD500阴性基因，并且PG4MD500数量的增加提供了累积效应。通过控制属性，包括基因家族、功能和启动子相似性，验证了这一观察结果。我们还观察到PG 4MD 500在链之间分布的不对称模式，其中PG 4MD 500在编码链中的频率通常高于模板链中的频率。进一步的分析表明，PG4MD500的存在及其链的不对称性与RNAP II在推定的TRR处的显著富集相关。在这些结果的基础上，我们提出了一个模型的G4 DNA介导的刺激转录的假设，即PG4MD500有助于基因转录，保持DNA在一个开放的构象，而PG4MD500的不对称分布大大降低了阻断模板链上的RNA聚合酶复合物的进展的可能性。我们的研究结果提供了G4 DNA在基因转录中的调节功能的全面视图。
G-quadruplex or G4 DNA, a four-stranded DNA structure formed in G-rich sequences, has been hypothesized to be a structural motif involved in gene regulation. In this study, we examined the regulatory role of potential G4 DNA motifs (PG4Ms) located in the putative transcriptional regulatory region (TRR, -500 to + 500) of genes across the human genome. We found that PG4Ms in the 500-bp region downstream of the annotated transcription start site (TSS; PG4M(D500)) are associated with gene expression. Generally, PG4M(D500)-positive genes are expressed at higher levels than PG4MD500-negative genes, and an increased number of PG4MD500 provides a cumulative effect. This observation was validated by controlling for attributes, including gene family, function, and promoter similarity. We also observed an asymmetric pattern of PG4MD500 distribution between strands, whereby the frequency of PG4MD500 in the coding strand is generally higher than that in the template strand. Further analysis showed that the presence of PG4MD500 and its strand asymmetry are associated with significant enrichment of RNAP II at the putative TRR. On the basis of these results, we propose a model of G4 DNA-mediated stimulation of transcription with the hypothesis that PG4MD500 contributes to gene transcription by maintaining the DNA in an open conformation, while the asymmetric distribution of PG4MD500 considerably reduces the probability of blocking the progression of the RNA polymerase complex on the template strand. Our findings provide a comprehensive view of the regulatory function of G4 DNA in gene transcription.