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Letter

Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription

State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, 10094, People’s Republic of China

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 PG4M_D500-negative genes, and an increased number of PG4M_D500 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 PG4M_D500 distribution between strands, whereby the frequency of PG4M_D500 in the coding strand is generally higher than that in the template strand. Further analysis showed that the presence of PG4M_D500 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 PG4M_D500 contributes to gene transcription by maintaining the DNA in an open conformation, while the asymmetric distribution of PG4M_D500 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.

² Corresponding author.

E-mail ninglbau{at}public3.bta.net.cn; fax 86-10-62733904.

[Supplemental material is available online at www.genome.org.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6905408

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