Figure 1.

The methylation transmission process of the MiAge model. (a) During a cell division, each of the two strands of a DNA molecule becomes a parent strand, which is used as a template to synthesize a daughter strand. During the intermediate post-replication stage, daughter strands are completely unmethylated, whereas parent strands have the same methylation patterns as before. Subsequently, methyl groups are added to cytosines. In this process, failure of maintenance and/or de novo methylation events can occur with certain probabilities. (b) All methylation transition events that happen within a cell division. At a CpG site, P_n is the methylation status (1 if methylated and 0 otherwise) of a pre-replication parent strand in the n^th cell generation; Q_n is the methylation status of a post-methylation parent strand; D_n is the methylation status of a post-methylation daughter strand; µ is the probability of maintaining methylation during a cell division; and δ^p and δ^d are the probabilities of de novo methylation event on the parent and daughter strand. Thus X_n = (Q_n+D_n)/2 is the mean methylation status of the double strands at a CpG site on one sister chromosome in the n^th cell generation in one cell.