Methylation gradient modeling. (A) Intercept and slope estimates from 68 p13E-11 to pLAM 5U reads from participant P1. The red line is the model estimate and the thin lines are the individual read estimates with a color scale for read-level % 5mC. The right panel shows the D4Z4 repeat-level methylation frequency (points) and the estimate (line) for each read, ordered by read-level % 5mC. (B) Intercept and slope estimates as in (A) from FSHD1, FSHD2 participants, and control subject C4 (see Table 2). (C) Model for gradient formation via basal D4Z4 methylation followed by unbalanced bidirectional spreading (colored arrows). (D) Predicted D4Z4 methylation levels from simulated basal methylation and spreading (red points) compared to observed values [blue points, mean methylation per repeat, data from (B)]. In the lower panel, the basal methylation and spreading parameters were reduced by a factor of 2.
