English: Global CpG Methylation Levels in the Mouse Germline, Somatic Tissues, and ESCs. The mouse germline undergoes two major waves of demethylation, the first in the early embryo where the paternal genome (blue) is actively demethylated prior to and during replication. Both the paternal and maternal (red) genomes passively lose methylation after this until the blastocyst stage (E3.5). The second wave of demethylation occurs in the primordial germ cells between E6.5 and E13.5 as they emerge from the epiblast. Methylation is then re-established in a sex-specific manner after E13.5 and the nongrowing (NG) oocyte stage, in males and females, respectively, eventually giving rise to mature gametic patterns. Naive and primed ESCs can be cultured from the ICM or be interchanged with each other (dashed line), by growth in either serum or 2i media, respectively. Only naive ESCs display low methylation (c. 30%) that corresponds to in vivo pluripotent tissues (shaded boxes on the far right). Erased cells display less than 10% methylation, whereas somatic tissues (derived from the E6.5 epiblast) show consistently high methylation around 70%–85%. The placenta is relatively demethylated compared to somatic tissues and is derived from the blastocyst trophectoderm (E3.5). In order to compare between genome-wide (Ficz et al., 2013; Hon et al., 2013; Kobayashi et al., 2012; Seisenberger et al., 2012; Shirane et al., 2013) and reduced representation bisulfite sequencing data sets (Smallwood et al., 2011; Smith et al., 2012), 100 kb probes not overlapping CpG islands were analyzed as previously (Ficz et al., 2013).