Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development

TLDR

The study proposes that methylation in somatic tissues stabilizes and reinforces prior regulatory events affecting gene activity, chromosome domains, and the X chromosome in females. After preimplantation demethylation, embryonic and extraembryonic lineages are progressively and independently remethylated to distinct final levels, with methylation persisting postgastrulation to potentially initiate or confirm differential programming in definitive germ layers. Stage‑ and tissue‑specific global demethylation and remethylation occur during embryonic development, with the egg genome markedly undermethylated, the sperm genome relatively methylated, and fetal germ cells remaining undermethylated, suggesting the germ lineage is set aside before extensive DNA methylation in fetal precursors.

Abstract

ABSTRACT This paper shows stage- and tissue-specific global demethylation and remethylation occurring during embryonic development. The egg genome is strikingly undermethylated and the sperm genome relatively methylated. Following a loss of genomic methylation during preimplantation development, embryonic and extraembryonic lineages are progressively and independently methylated to different final extents. Methylation continues postgastrulation and hence could be a mechanism initiating, or confirming, differential programming in the definitive germ layers. It is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome (in females). Fetal germ cell DNA is markedly undermethylated and we favour the idea that the germ lineage is set aside before the occurrence of extensive methylation of DNA in fetal precursor cells.