GC skew is a conserved property of unmethylated CpG island promoters across vertebrates.
GC skew is a conserved property of unmethylated CpG island promoters across vertebrates.
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DOI：
10.1093/nar/gkv811
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发表时间：
2015-11-16
影响因子：
14.9
通讯作者：
Chédin F
中科院分区：
文献类型：
--
作者：
Hartono SR;Korf IF;Chédin F
GC偏斜是鸟嘌呤和胞嘧啶分布中链不对称性的量度。GC偏斜有利于R环，R环是一种三链核酸结构，在RNA链与DNA链退火时形成，产生持久的RNA：DNA杂合体。先前的研究表明，GC偏斜普遍存在于数千个人类CpG岛（CGI）启动子和转录终止区，这些区域对应于R环形成的热点。在这里，我们调查了60个测序脊索动物基因组中GC偏斜模式的保守性。我们报告，GC倾斜是一个保守的序列特征的CGI启动子类在脊椎动物。此外，我们发现，启动子GC歪斜峰在外显子1/内含子1交界处，它是高度相关的基因年龄和CGI启动子强度。我们的数据还表明，GC偏斜是一系列脊椎动物物种中未甲基化的CGI启动子的预测，并且它赋予具有中间CpG密度的启动子显著的DNA低甲基化。最后，我们观察到，终端GC偏斜是保守的脊椎动物基因的一个子集，往往是位于显着更接近其下游邻居，与R-环的形成在转录终止的作用一致。
GC skew is a measure of the strand asymmetry in the distribution of guanines and cytosines. GC skew favors R-loops, a type of three stranded nucleic acid structures that form upon annealing of an RNA strand to one strand of DNA, creating a persistent RNA:DNA hybrid. Previous studies show that GC skew is prevalent at thousands of human CpG island (CGI) promoters and transcription termination regions, which correspond to hotspots of R-loop formation. Here, we investigated the conservation of GC skew patterns in 60 sequenced chordates genomes. We report that GC skew is a conserved sequence characteristic of the CGI promoter class in vertebrates. Furthermore, we reveal that promoter GC skew peaks at the exon 1/ intron1 junction and that it is highly correlated with gene age and CGI promoter strength. Our data also show that GC skew is predictive of unmethylated CGI promoters in a range of vertebrate species and that it imparts significant DNA hypomethylation for promoters with intermediate CpG densities. Finally, we observed that terminal GC skew is conserved for a subset of vertebrate genes that tend to be located significantly closer to their downstream neighbors, consistent with a role for R-loop formation in transcription termination.