Fig. 1: A dynamical model and cellular system to infer methylation and demethylation rates.

a Graphic representation of methylation and demethylation rates. The orange and green arrows represent k_de and k_me, respectively. The enzymes responsible for influencing rates are noted. The ratio of rates determines overall methylation levels (Equation (1) below). b Example steady-state methylation levels resulting from different k_me (green) and k_de (orange) combinations. Higher methylation levels are established when k_me is larger than k_de, while low methylation levels represent the opposite. CpGs with the same steady state can have different rates as shown here for 50%. c Theoretical trace of methylation loss over time post Cre transduction for two CpGs with similar steady states. d Cellular system for genetic ablation of k_me. Dnmt3a and Dnmt3b with loxP sites flanking catalytic exons. Cre protein transduction allows for efficient genetic deletion of all four alleles. e Heatmap of methylation levels for 405 CpGs as measured by amplicon bisulfite sequencing. The left half represents methylation levels for triplicate experiments measured 0, 4, 8, 10, 13, 17, and 29 days post Cre transduction. The right half represents triplicates for mock-treated samples. f CpGs were binned based on starting methylation in 10% increments, and the mean decay over triplicates for Cre-transduced samples (left) and mock samples (right) are shown. g Dynamical model for DNA methylation and implementation of the exponential dampening factor k_e for affecting k_me over time (Eqs. (2)–(4)). See text and “Methods” for details.