DNA methylation reprogramming of genomic imprints in the mammalian germline: A TET-centric view

The mammalian genome undergoes extensive epigenetic reprogramming twice during development, once during gestation when primordial germ cells (PGCs) are specified from somatic cells and a second time after fertilization in the preimplantation embryo. PGC differentiation into germ cells involves DNA demethylation and subsequent remethylation. DNA demethylation takes place in two waves in the mouse germline, an early phase where most of the genome is demethylated by replication coupled passive demethylation, and a second phase predominated by active DNA demethylation. Imprinted genes, CpG islands on the inactive X chromosome of females, and germline-specific genes are among those loci that are demethylated late. The Ten-Eleven Translocation (TET) family of 5 mC dioxygenases has emerged as active demethylating enzymes that are critical to achieving a DNA hypomethylated state, with TET1 being the most important for imprinted genes. Here, we discuss DNA methylation dynamics in the mammalian genome, with a particular emphasis on DNA demethylation in the germline and the requirement for TET1 in imprinted gene reprogramming.