Whole genome experimental maps of DNA G-quadruplexes in multiple species

Abstract

Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K + conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PDS). We discuss the various structural features of the experimentally observed G-quadruplexes (OQs), highlighting differences in their prevalence and enrichment across species. Our study describes diversity in sequence composition and genomic location for the OQs in the different species and reveals that the enrichment of OQs in gene promoters is particular to mammals such as mouse and human , among the species studied. The multi-species maps have been made publicly available as a resource to the research community. The maps can serve as blueprints for biological experiments in those model organisms, where G4 structures may play a role.

Alternative splicing modulation by G-quadruplexes

“…G4-seq utilizes the fact that stable G4s can stall the DNA polymerase in vitro, thereby allowing high throughput sequencing to be used to detect G4s at high resolution. We first measured the distribution of G4s relative to the splice sites for HEK-293T cells in Pyridostatin (PDS) and K + treatments from (Marsico et al 2019). In both conditions, we observed an enrichment of G4-seq peaks relative to the 3′ss and 5′ss, but with a more pronounced G4 enrichment in PDS treatment compared to K + treatment (Fig 1b).…”

“…To evaluate if the G4 motifs that were enriched near splice sites lead to the formation of DNA G4 structures in vitro, we analyzed previously published G4-seq data (Chambers et al 2015), (Marsico et al 2019). G4-seq utilizes the fact that stable G4s can stall the DNA polymerase in vitro, thereby allowing high throughput sequencing to be used to detect G4s at high resolution.…”

Genome duplication inLeishmania majorrelies on DNA replication outside S phase

“…ChIP data for AcH3, baseJ and KKT1 were previously published (44,45,47). Experimental mapping of G4quadruplex in L. major was published previously (53). Whole genome sequencing used for MFA-seq data presented in Figures 1, 2 and 3 was taken from (15).…”

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

“…[28] The maturity of bioinformatics allows the mining of whole genomes to locate potential G4-forming sequences, identifying hundreds of thousands of occurrences in the genomes of humans and other organisms, [29][30][31][32] whilst cutting-edge sequencing methods have validated the existence of such quadruplexes experimentally in a number of species. [33] Meanwhile, progress in biology has delivered ever increasing evidence for the role of these sequences in life, from organism development, through to epigenetic regulation and their role in health and disease. [34,35] Indeed, various therapeutic hypotheses have been proposed, such as targeting G4s to inhibit the transcription of oncogenes [36,37] (Figure 2) or by targeting the G4 sequence in chromosome telomeres.…”