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Abstract
Genome-wide epigenetic reprogramming in mammalian germ cells, zygote and early embryos,
plays a crucial role in regulating genome functions at critical stages of development.
We show here that mouse primordial germ cells (PGCs) exhibit dynamic changes in epigenetic
modifications between days 10.5 and 12.5 post coitum (dpc). First, contrary to previous
suggestions, we show that PGCs do indeed acquire genome-wide de novo methylation during
early development and migration into the genital ridge. However, following their entry
into the genital ridge, there is rapid erasure of DNA methylation of regions within
imprinted and non-imprinted loci. For most genes, the erasure commences simultaneously
in PGCs in both male and female embryos, which is completed within 1 day of development.
Based on the kinetics of this process, we suggest that this is an active demethylation
process initiated upon the entry of PGCs into the gonadal anlagen. The timing of reprogramming
in PGCs is crucial since it ensures that germ cells of both sexes acquire an equivalent
epigenetic state prior to the differentiation of the definitive male and female germ
cells in which new parental imprints are established subsequently. Some repetitive
elements, however, show incomplete erasure, which may be essential for chromosome
stability and for preventing activation of transposons to reduce the risk of germline
mutations. Aberrant epigenetic reprogramming in the germ line would cause the inheritance
of epimutations that may have consequences for human diseases as suggested by studies
on mouse models.
Copyright 2002 Elsevier Science Ireland Ltd.