Université Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, France.
Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nat Commun. 2023 Aug 10;14(1):4843. doi: 10.1038/s41467-023-40441-4.
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.
脊椎动物基因组的复制受到严格调控，以确保准确复制，但我们对遗传和表观遗传因素在这种调控中的相互作用的理解仍不完整。在这里，我们研究了在脊椎动物中，富集在基因启动子和复制起点的三个元素（可能形成 G-四联体的富含鸟嘌呤的基序（pG4s）、无核小体区（NFRs）和组蛋白变体 H2A.Z）在复制起点引发中的作用。我们表明，在同一 DNA 链上的两个 pG4s（二聚体 pG4s）足以在不诱导转录的情况下，在禽类 DT40 细胞中诱导有效的最小复制起点的组装。复制起点的二聚体 pG4s与紧邻精确定位的核小体形成 NFR 相关，这些核小体在这个最小起点和全基因组中富含 H2A.Z。因此，我们的数据表明，二聚体 pG4s 对于脊椎动物基因组的组织和复制很重要。它支持了这样一种假设，即靠近 NFR 的核小体是真核生物中复制起点形成的共同信号。
