Fig. 7

Trans-generational maintenance of CpG methylation status. a Methylation dynamics of two CpGs at a locus with low affinity for TFs present in E14.5m PGCs and ESCs. Such sites are hypermethylated in sperm but undergo de-methylation upon fertilization. During the re-methylation phase in ESCs, no TF binds and the site becomes re-methylated. In PGCs, it again becomes de-methylated, only to become re-methylated again starting around E14.5 in male PGCs, in which the site is not bound by a TF. Hypermethylation is maintained in sperm and adult somatic tissues. b Methylation dynamics of two CpGs near a high-affinity binding site for at least one TF present in E14.5m PGCs and ESCs. The site is hypomethylated in E14.5m PGCs and is bound by a TF; it remains hypomethylated through sperm maturation. This hypomethylated state is passed to the next generation upon fertilization. In ESCs, this site again binds a TF and subsequently remains hypomethylated. The site is hypomethylated in successive generations in both sperm and adult somatic tissues. c Methylation dynamics of a pair of CpGs at an IAP-like DNA element. These sites are capable of resisting global de-methylation, at least in part, upon fertilization and in PGCs. They remain partially methylated in the ICM and E13.5m PGCs and are hypermethylated at all other stages of development. These sites tend to have a high affinity for TFs in E14.5m PGCs and ESCs, but rarely become bound by them, possibly due the high DNA methylation levels. Thus, they remain persistently hypermethylated in sperm and adult somatic tissues