Dimeric G-quadruplex motifs determine a large fraction of strong replication origins in vertebrates

Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce assembly of an efficient minimal replication origin without inducing transcription, and that dimeric pG4s in replication origins are located in an NFR next to well-positioned nucleosomes enriched in H2A.Z. Thus, our data suggest a crucial role for dimeric pG4s in the organization and duplication of vertebrate genomes.