G4 motifs in human genes

Abstract

The G4 motif, G(≥3) N(x) G(≥3) N(x) G(≥3) N(x) G(≥3) , is enriched in some genomic regions and depleted in others. This motif confers the ability to form an unusual four-stranded DNA structure, G4 DNA. G4 DNA is associated with genomic instability, which may explain depletion of G4 motifs from some genes and genomic regions. Conversely, G4 motifs are enriched downstream of transcription start sites, where they correlate with pausing. The uneven distribution of G4 motifs in the genome strongly suggests that mechanisms of selection act not only on one-dimensional genomic sequence, but also on structures formed by genomic DNA. The biological roles of G4 structures illustrate that, to understand genome function, it is important to consider the dynamic structural potential implicit in the G4 motif.

Figure 1

G-quartets and G4 DNA. (A) G-quartet formed by interactions among four guanine bases in DNA or RNA. (B) Intramolecular G4 DNA. The diagram illustrates two of the possible structures formed by the sequence G₃N₃G₃N₂G₄N₂G₅.

Figure 2

Formation of G4 DNA during transcription or replication. Right, transcription of two adjacent G4 motifs results in formation of a G-loop, containing a stable RNA/DNA hybrid (gray) and G4 DNA on the nontemplate strand. Left, G4 DNA forms on the template for lagging-strand replication.

Figure 3

Distribution of G4 motifs in human genes. Percentage of genes with one or more G4 motifs per 100 bp interval was calculated for the nontemplate and template strands of the indicated regions flanking the transcription start site (TSS, top); at the 5′ ends of the first or second introns (middle); and at the 5′-ends of the 5′-UTR and coding region, or the 3′-ends of the coding region and 3′-UTR. Exons, shaded; 3′-UTR, hatched. Nontemplate and template strands are represented by solid and dashed lines, respectively. UTR, untranslated region.