Figure 6: Combinations of global and local nucleosomal cross-talks recapitulate the observed kinetics.

(a) Positive feedbacks in the recruitment of histone-modifying enzymes. Nucleosomes exist in three states, methylated (M; red), unmodified (U; grey), or acetylated (A; blue). Methylated and acetylated nucleosomes recruit modifying enzymes capable of modifying the immediate neighbours of the nucleosome to which they bind (thin dashed arrows: local feedback) and, for A to U, more distant nucleosomes as well (thick arrow: global feedback). The evolution of a 23-kb region representing the mating-type region with two reporters was simulated, using parameters and a source of methylation at cenH (cyan) as described in the text. (b) Two model simulations with identical parameters of the dynamics in nucleosome modification profile over the 23-kb mating-type region following the re-introduction of Clr4 at time 0. (c) Times of silencing for the Kint2 (cyan) and (EcoRV) (green) positions in the simulations occurred with the kinetics measured in vivo at these two locations. (d) Fraction of cells with none, one or both genes active as function of time. (e) Distribution of epigenetic states for the ΔK mutant with an epigenetic stability compatible with experimental measurements.