text: The newly formed primordial germ cells (PGC) in the implanted embryo devolve from the somatic cells at about day 7 of embryogenesis in the mouse.  At this point the PGCs have high levels of methylation. These cells migrate from the epiblast toward the gonadal ridge. As reviewed by Messerschmidt et al., the majority of PGCs are arrested in the G phase of the cell cycle while they migrate toward the hindgut during embryo days 7.5 to 8.5. Then demethylation of the PGCs takes place in two waves.  There is both passive and active, TET-dependent demethylation of the primordial germ cells.  At day 9.5 the primordial germ cells begin to rapidly replicate going from about 200 PGCs at embryo day 9.5 to about 10,000 PGCs at day 12.5.  During days 9.5 to 12.5 DNMT3a and DNMT3b are repressed and DNMT1 is present in the nucleus at a high level.  But DNMT1 is unable to methylate cytosines during days 9.5 to 12.5 because the UHRF1 gene (also known as NP95) is repressed and UHRF1 is an essential protein needed to recruit DNMT1 to replication foci where maintenance DNA methylation takes place.  This is a passive, dilution form of demethylation. 
  In addition, from embryo day 9.5 to 13.5 there is an active form of demethylation.  As indicated in the Figure of the demethylation pathway above, two enzymes are central to active demethylation.  These are a ten-eleven translocation (TET) methylcytosine dioxygenase and thymine-DNA glycosylase (TDG).  One particular TET enzyme, TET1, and TDG are present at high levels from embryo day 9.5 to 13.5, and are employed in active TET-dependent demethylation during gametogenesis.  PGC genomes display the lowest levels of DNA methylation of any cells in the entire life cycle of the mouse by embryonic day 13.5.