Extended Data Figure 5: Suggested models implicating 5mC oxidation in DNA demethylation of gonadal PGCs.

a, A model of oxidation followed by passive dilution predicts a positive correlation between the extent to which the combined levels of 5mC and 5hmC decrease between two stages (as determined by WGBS) and the total level of 5hmC at both the stage immediately preceding and following the decrease. b, A model implicating 5mC oxidation in triggering DNA demethylation via an active mechanism predicts a positive correlation between the extent to which the combined levels of 5mC and 5hmC decrease between two stages (as determined by WGBS) and the relative levels of 5hmC in the stage immediately preceding this decrease, as further oxidation of 5hmC to 5-formylcytosine (5fC) is the rate-limiting step in the full oxidation of 5mC to 5-carboxylcytosine (5caC) (ref. 39). c, A model implicating oxidation of 5mC in safeguarding DNA hypomethylation following the major wave of DNA demethylation predicts that regions where the majority of DNA methylation has been lost between two stages (that is, those that are newly hypomethylated) will have high relative levels of 5hmC in the stage immediately after the major wave of DNA demethylation in order to remove residual methylation and/or aberrant de novo methylation. Thus, a limited correlation between the extent to which the combined levels of 5mC and 5hmC decrease between two stages (as determined by WGBS) and the relative levels of 5hmC in the stage immediately following this decrease may also be seen.