High-throughput sequencing of DNA G-quadruplex structures in the human genome
High-throughput sequencing of DNA G-quadruplex structures in the human genome
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DOI：
10.1038/nbt.3295
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发表时间：
2015-08-01
影响因子：
46.9
通讯作者：
Balasubramanian, Shankar
中科院分区：
文献类型：
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作者：
Chambers, Vicki S.;Marsico, Giovanni;Balasubramanian, Shankar
G-四链体（G4）是在富含鸟嘌呤的DNA或RNA序列内形成的核酸二级结构。G4形成可以影响染色质结构和基因调控，并且与基因组不稳定性、遗传疾病和癌症进展相关（1-4）。在这里，我们提出了一种基于高分辨率测序的方法来检测人类基因组中的G4。我们鉴定了716，310个不同的G4结构，其中451，646个未通过计算方法预测（5-7）。这些包括以前未表征的非典型长环和凸起结构（8，9）。我们观察到在功能区域，如5'非翻译区和剪接位点，以及在以前没有预测包含这些结构的基因（如BRCA 2）中有高的G4密度。G4形成与癌基因、肿瘤抑制因子和与癌症发展相关的体细胞拷贝数改变显著相关（10）。因此，本研究中鉴定的G4可能是癌症干预的有希望的靶点。
G-quadruplexes (G4s) are nucleic acid secondary structures that form within guanine-rich DNA or RNA sequences. G4 formation can affect chromatin architecture and gene regulation and has been associated with genomic instability, genetic diseases and cancer progression(1-4). Here we present a high-resolution sequencing-based method to detect G4s in the human genome. We identified 716,310 distinct G4 structures, 451,646 of which were not predicted by computational methods(5-7). These included previously uncharacterized noncanonical long loop and bulged structures(8,9). We observed a high G4 density in functional regions, such as 5' untranslated regions and splicing sites, as well as in genes previously not predicted to contain these structures (such as BRCA2). G4 formation was significantly associated with oncogenes, tumor suppressors and somatic copy number alterations related to cancer development(10). The G4s identified in this study may therefore represent promising targets for cancer intervention.