Regulation of paternally imprinted (blue), maternally imprinted (red), and nonimprinted (yellow) DNA methylation during early embryo development and gametogenesis. Dashed arrows, dotted arrows, and thin arrows indicate demethylation, de-novo methylation, and unmethylated status, respectively. (1) Sex-specific imprints are established in the mature oocyte and in the sperm. Shortly after fertilization, genome-wide demethylation occurs at nonimprinted genomic loci. (2) De-novo methylation at nonimprinted regions on DNA. This epigenetic reprogramming enables cell differentiation by turning different genes on and off in different cells. After that stage, maternal and paternal imprints and nonimprinted methylation are maintained in somatic cells of the embryo throughout life (not shown in the figure). (3) Another wave of demethylation initiates at the imprinted DMRs in primordial germ cells of the embryo. (4) Biparental imprints are erased in the germ cells. (5) Paternal imprint acquisition starts in the spermatogonia of the male fetus, whereas DMRs remain unmethylated in the oocytes of the female fetus. (6) Paternal imprint acquisition is completed in the germ cells of the male fetus and maintained throughout life. (7) Imprinted DMRs remain unmethylated in the primordial oocytes in female embryo. (8) After puberty, maternal imprints are established during oocyte growth.