Distinct Modes of Regulation by Chromatin Encoded through Nucleosome Positioning Signals
Figure 13
Nucleosome positioning signals may explain DNA replication efficiency.
(A) Nucleosomes are depleted from origins of DNA replication in S. cerevisiae. Shown is the average number of nucleosome reads in our data (cyan) per basepair around 82 annotated origins of replication from yeast [63]. Note that the typical length of the nucleosome depleted regions is greater around replication origins than it is around transcription start sites (e.g., compare to the length of the depleted region from Figure 9A and 9B). Also shown is the average nucleosome occupancy predicted by the nucleosome positioning model that we developed here (red), per basepair around the same 82 origins. (B) Nucleosome depletion is predicted around replication origins from S. pombe. Shown is the average nucleosome occupancy predicted by our nucleosome positioning model (red), per basepair in the vicinity of 386 annotated origins of replication from S. pombe [61]. The exceptionally large length of the nucleosome depleted regions around these replication origins may reflect the lower resolution with which S. pombe origins are mapped (∼3 Kb), compared to their S. cerevisiae analogs. (C) Shown is a schematic illustration of replication origins with low and high replication efficiency. The schematic illustrates that in the low efficiency origins (“type I”, left column), binding sites for the replication machinery are measurably occupied by both their replication factors and nucleosomes (in a cell population), suggesting that their low efficiency results from competition between nucleosomes and factors for DNA access. In contrast, the high efficiency origins (“type II”, right column) exhibit a characteristic nucleosome-depleted region that allows the replication machinery to access the origins and replicate the DNA with high efficiency. (D) Replication origins from S. pombe that have large nucleosome depleted regions are utilized with greater efficiency. We computed the average (predicted) nucleosome occupancy in 500 bp windows within the 3 kb region surrounding each of the 386 annotated origins from (B). With each replication origin, we associated the lowest nucleosome occupancy in any of its 500 bp windows. The 3 kb region was selected since the data on replication efficiency have a ∼3 kb resolution [61]; 500 bp windows were selected since these are the typical lengths of the nucleosome depleted regions over origins in S. cerevisiae, where origins are mapped with greater accuracy. Using these computed lowest nucleosome occupancies for origins, we grouped together the 100 origins that have the highest of these values (type I), and the 100 origins that have the lowest of these values (type II). For each of these two groups, shown is the fraction of its origins (y-axis) whose efficiency of replication initiation as measured in [61] is within the k most efficient origins (x-axis; expressed as fraction), for all possible values of k. Measurements of efficiency of replication initiation are presented in their ranked value.