Epigenetic cell memory: The gene’s inner chromatin modification circuit
Fig 2
Reactions associated with the chromatin modification circuit motifs.
Each reaction is associated with a number, which is referred to in the main text. Specifically, reactions ⓪, ①, ②, ③, ⑩ and ⑪ describe de novo establishment. Reactions ④ and ⑤ describe auto-catalysis, wherein a modification recruits writers of the same modification to nearby nucleosomes. Reactions ⑮ and ⑯ describe cross-catalysis, wherein DNA methylation recruits writers of repressive histone modifications and viceversa, respectively. Reactions ⑥, ⑦, and ⑫ represent basal erasure while reactions ⑧, ⑨, ⑬, and ⑭ represent recruited erasure, wherein competing modifications recruit erasers of each other. The different colored lines delimit the sets of reactions that take place for each of the circuit motifs shown in Fig 1 and Figs B and C in S1 File. Specifically, Fig B depicts the circuit between activating histone modifications and DNA methylation and Fig C depicts the circuit among repressive modifications. Here, we use one-step enzymatic reaction models [36] to capture histone and DNA modifications. In the bottom-right corner, we indicate how the reaction rate constants depend on the amount of writers and erasers, in which f(⋅) is a generic increasing function. Here, η and are between 0 and 1 and defined in Section “Models”. Specifically, η = 1 in the absence of DNMT1 and
in the absence of MBD (see Section 1 in S1 File for the detailed form of the reaction constants and their derivation).