Fig. 4.

Alterations in methylation status during development. During embryonic development and gonadal sex determination, primordial germ cells undergo genome-wide demethylation, which erases previous parental-specific methylation marks that regulate imprinted gene expression. In the male germ line, paternal methylation marks in imprinted genes are laid down in developing gonocytes that will develop into spermatogonia. The female germ line establishes maternal methylation marks in imprinted genes at a later stage. After fertilization, the paternal genome is actively demethylated, whereas the maternal genome undergoes passive demethylation (176). Genome-wide remethylation occurs on both parental genomes before implantation. However, imprinted genes maintain their methylation marks throughout this reprogramming, allowing for the inheritance of parental-specific monoallelic expression in somatic tissues throughout adulthood. [Reprinted with permission from R. L. Jirtle and M. K. Skinner: Nat Rev Genet 8:253–262, 2007 (62). © 2007 Macmillan Publishers Ltd.]