Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine

Abstract

Epigenetic Controls: Germ cells in mammals give rise to sperm and eggs. During their development, germ cells undergo extensive epigenetic reprogramming, including global DNA demethylation, which is vital for the totipotency of the developing embryo. Hackett et al. (p. 448 ) show that the enzymes Tet1 and Tet2 are involved in the demethylation of individual genes and in imprinted gametic differentially methylated regions. The enzymes were also responsible for the global conversion of CpG methylation to 5-hydroxymethylcytosine, which then progressively declines. The findings suggest that demethylation can occur by replication-coupled dilution, although active mechanisms cannot be excluded. A small number of loci escape demethylation, providing a possible mechanistic basis for transgenerational inheritance.