Replication dependency of DNA methylation reprogramming in the zygote. (A) DNA methylation patterns (for explanation see Figure
1) and (B) absolute DNA methylation level and percentage of hemimethylated CpG dyads in relation to all methylated CpG dyads of L1 and mSat in +/- aphidicolin-treated (+/- replication-blocked) PN4-5 zygotes. Aphidicolin treatment leads to diminished DNA demethylation. (C,D) DNA methylation patterns of replicates (rep) and (C) absolute DNA methylation level of SAMase-treated early (pre-replicative) two-cell embryos. SAMase diminishes all methylation events that are dependent on S-adenosyl-methionine (SAM). The patterns were compared with those of in silico replicated zygotes with no DNA methylation maintenance (see Methods). The DNA methylation profiles of the biological replication without methylation events (SAMase-treated two-cell embryos) are very similar to those events simulated in silico without methylation.