The impact of nucleosome positioning on the organization of replication origins in eukaryotes

The distribution of DNA replication origins (ORIs) on eukaryotic chromosomes is nonrandom, but the reasons behind this are not well understood. Previous studies have suggested a prominent role of transcriptional activity in determining the ORI organization. Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution. Combining genome-wide data on nucleosome positioning and ORI organization in yeast and humans, we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication. However, contrary to priori claims, the impact of transcriptional activity is considerably weaker than previously proposed and could partly be explained by our nucleosome exclusion model. We propose that the ORI organization imposed by nucleosome positioning is phylogenetically widespread in eukaryotes.