Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes.
Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes.
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DOI：
10.1093/nar/gkm1138
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发表时间：
2008-03
影响因子：
14.9
通讯作者：
Maizels, Nancy
中科院分区：
文献类型：
--
作者：
Eddy, Johanna;Maizels, Nancy
为了了解 G 四链体形成的潜力如何影响基因表达的调控，我们检查了 18 217 个人类 RefSeq 基因的转录起始位点 (TSS) 的 2 kb，区分模板链和非模板链的贡献。 TSS 上游和下游区域均富含 G，但下游区域在非模板链上表现出明显的 G 丰富性偏向。 TSS 上游的 G 丰富度和 G 四链体形成的潜力大部分源自双链 DNA 中明确定义的规范调控基序的存在，包括作为调控甲基化位点的 CpG 二核苷酸，以及转录因子 SP1 识别的基序。这挑战了 TSS 上游四链体形成有助于基因表达调控的观点。 TSS 的下游，G 丰富度集中在第一个内含子和非模板链上，其中在近 3000 个 (16%) 人类 RefSeq 基因中发现了具有形成 G 四链体结构潜力且无法用已知调控基序解释的多态性序列元件，并且在青蛙中是保守的。这些元件原则上可以被识别为 DNA 或 RNA，为转录或 RNA 加工水平的调控提供结构目标。
To understand how potential for G-quadruplex formation might influence regulation of gene expression, we examined the 2 kb spanning the transcription start sites (TSS) of the 18 217 human RefSeq genes, distinguishing contributions of template and nontemplate strands. Regions both upstream and downstream of the TSS are G-rich, but the downstream region displays a clear bias toward G-richness on the nontemplate strand. Upstream of the TSS, much of the G-richness and potential for G-quadruplex formation derives from the presence of well-defined canonical regulatory motifs in duplex DNA, including CpG dinucleotides which are sites of regulatory methylation, and motifs recognized by the transcription factor SP1. This challenges the notion that quadruplex formation upstream of the TSS contributes to regulation of gene expression. Downstream of the TSS, G-richness is concentrated in the first intron, and on the nontemplate strand, where polymorphic sequence elements with potential to form G-quadruplex structures and which cannot be accounted for by known regulatory motifs are found in almost 3000 (16%) of the human RefSeq genes, and are conserved through frogs. These elements could in principle be recognized either as DNA or as RNA, providing structural targets for regulation at the level of transcription or RNA processing.
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