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首页> 外文期刊>Nucleic Acids Research >Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae.
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Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae.

机译：酿酒酵母中潜在的G-四链体形成序列的基因组分布和功能分析。

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摘要

Although well studied in vitro, the in vivo functions of G-quadruplexes (G4-DNA and G4-RNA) are only beginning to be defined. Recent studies have demonstrated enrichment for sequences with intramolecular G-quadruplex forming potential (QFP) in transcriptional promoters of humans, chickens and bacteria. Here we survey the yeast genome for QFP sequences and similarly find strong enrichment for these sequences in upstream promoter regions, as well as weaker but significant enrichment in open reading frames (ORFs). Further, four findings are consistent with roles for QFP sequences in transcriptional regulation. First, QFP is correlated with upstream promoter regions with low histone occupancy. Second, treatment of cells with N-methyl mesoporphyrin IX (NMM), which binds G-quadruplexes selectively in vitro, causes significant upregulation of loci with QFP-possessing promoters or ORFs. NMM also causes downregulation of loci connected with the function of the ribosomal DNA (rDNA), which itself has high QFP. Third, ORFs with QFP are selectively downregulated in sgs1 mutants that lack the G4-DNA-unwinding helicase Sgs1p. Fourth, a screen for yeast mutants that enhance or suppress growth inhibition by NMM revealed enrichment for chromatin and transcriptional regulators, as well as telomere maintenance factors. These findings raise the possibility that QFP sequences form bona fide G-quadruplexes in vivo and thus regulate transcription.
机译：尽管在体外进行了充分研究，但G-四链体（G4-DNA和G4-RNA）的体内功能才刚刚开始被定义。最近的研究表明在人，鸡和细菌的转录启动子中富集了具有分子内G-四链体形成潜能（QFP）的序列。在这里，我们调查了酵母基因组的QFP序列，并在上游启动子区域中类似地发现了这些序列的强富集，以及在开放阅读框（ORF）中弱但显着的富集。此外，有四个发现与QFP序列在转录调控中的作用一致。首先，QFP与组蛋白占有率低的上游启动子区域相关。第二，用N-甲基中卟啉IX（NMM）处理细胞，在体外选择性地结合G-四链体，导致具有QFP的启动子或ORF显着上调基因座。 NMM还引起与核糖体DNA（rDNA）功能相关的基因座的下调，而核糖体DNA（rDNA）本身具有较高的QFP。第三，在缺少G4-DNA解旋解旋酶Sgs1p的sgs1突变体中，具有QFP的ORF被选择性下调。第四，对通过NMM增强或抑制生长抑制的酵母突变体进行的筛选显示，染色质和转录调节剂以及端粒维持因子富集。这些发现增加了QFP序列在体内形成真正的G-四链体从而调节转录的可能性。

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