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.