Fig 3. DNA remethylation Distributive (A), Processive (B) and Collaborative mechanisms (C).

Hemimethylated sites (e.g. sites that can be remethylated) are indicated as empty pentagons, while methylated sites are represented as red-filled pentagons. Unmethylated sites are not represented in the scheme. In the Distributive model DNMT1 binds to a hemimethylated CpG site, incorporates SAM, and catalyzes methylation. Methylation and release of both DNMT1 and SAH occur in a single step. In the Processive model, after methylation DNMT1 can diffuse towards its immediate neighbor sites either upstream (U) or downstream (D). In the Collaborative model, once DNMT1 is bound to a hemimethylated CpG, a second DNMT1 molecule can be recruited onto nearby CpG sites. A distance function adapted from [42] favors recruitment at nearer CpGs.