RESUMEN
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 in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce the assembly of an efficient minimal replication origin without inducing transcription in avian DT40 cells. Dimeric pG4s in replication origins are associated with formation of an NFR next to precisely-positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest that dimeric pG4s are important for the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.
Asunto(s)
G-Cuádruplex , Nucleosomas , Animales , Nucleosomas/genética , Origen de Réplica/genética , Replicación del ADN/genética , Histonas/genética , Histonas/metabolismo , Vertebrados/genética , Vertebrados/metabolismoRESUMEN
The correct duplication of the human genome is under the control of a spatiotemporal program that determines where and when replication forks start. This regulation thus mainly operates on replication start sites named replication origins. During the S-phase, about 50 000 origins fire in one human cell. However, the normal or perturbed progression of replication forks also strongly impacts on replication. Recently, several studies have put forward the role of a noncanonical DNA structure, the G-quadruplex, in the control of genome duplication. In this review, we describe the major impact of this structure on starting points and on the progression of replication forks.