Resetting for the Next Generation Michael Cowley, Rebecca J. Oakey  Molecular Cell  Volume 48, Issue 6, Pages 819-821 (December 2012) DOI: 10.1016/j.molcel.2012.12.007 Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 1 DNA Methylation Dynamics during Developmental Reprogramming After fertilization, the paternal genome (blue line) is demethylated rapidly by active mechanisms, while the maternal genome (red line) is passively demethylated. Differentially methylated regions (DMRs) associated with imprinted genes are protected from this erasure (dashed green line). De novo methylation occurs postimplantation (black line), but PGCs are not specified until the epiblast stage (shading at top of figure). This methylation must be reset in PGCs. From e6.5, the figure shows the methylation dynamics in the cells that form the germline only. Most sequences are demethylated in PGCs by e9.5. A subset of sequences are late demethylaters and are not reprogrammed until after PGC migration. These include, but are not limited to, the imprinted DMRs. IAPs are resistant to demethylation during both the postfertilization and the PGC reprogramming waves. Variably erased CGIs (VECs) can resist erasure during PGC reprogramming, but their methylation status during postfertilization reprogramming is unclear. Following sex determination, de novo methylation of the germ cells occurs, but the dynamics are sex specific. Methylation is completed in prospermatogonia before birth, whereas methylation of oocytes is established during the growth phase, after birth. In adulthood, the gametes are appropriately methylated to form a new zygote and restart the cycle of methylation dynamics. Shown below are the developmental windows examined by three key studies, with the specific time points analyzed indicated. blast., blastocyst. d5, day 5 oocytes. GV, germinal vesicle oocytes. MII, metaphase II oocytes. Molecular Cell 2012 48, 819-821DOI: (10.1016/j.molcel.2012.12.007) Copyright © 2012 Elsevier Inc. Terms and Conditions