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Diffusion controls local versus dispersed inheritance of histones during replication and shapes epigenomic architecture

Fig 2

Differential histone diffusivity between chromatin compartments explains histone dilution kinetics during replication.

(A) A model of histone dilution at the replication fork incorporating the DAD hypothesis (Model 1). Each row of the parent matrix represents a different DNA locus (either on the same or on different chromosomes) and columns represent histone sites. Histones are shown as green spheres, with the j = 1 histones shown larger to indicate diffusion within rows of the same column. The yellow stars represent biotin tags on the histones at one particular locus of interest R*, mimicking the initial conditions of the experimental protocol in Escobar et al [28]. The arrows show examples of possible movement of histones between loci from the parent to either daughter or . The probabilities of these transitions are based upon laws of diffusion, which accounts for the distance between parent and daughter loci x_i,i′ = |i − i′| (details in Methods and SI). (B) Flowchart of one run of the simulation for multiple cell cycles. Histone are distributed from parent to the two daughter matrices based on the laws of diffusion, and the process repeated many times. Empty spots arising out of histone dilution are filled with untagged histones, thereby leading to a decrease in number of tagged histones at the locus R*. (C) Comparison of model (pink dashed lines) with experimental results [28] (green solid lines) for both active and repressed genes. Results from three active genes (Pou5f1, Nanog, Ccna2) and three repressed genes (Meis2, Hoxc6, Ebf1) are shown here. The model results represent best fit curves, with the diffusion constant D as the only free parameter. (D) As expected, fitted diffusion constants from panel (C) are higher for active genes than repressed genes, demonstrating the reasonability of our model.

doi: https://doi.org/10.1371/journal.pcbi.1011725.g002