During embryogenesis and gametogenesis, the DNA methyltransferases Dnmt3A and Dnmt3B establish the genome-wide methylation patterns that are essential for mammalian development and reproduction. The catalytically inert Dnmt3-like (Dnmt3L) is known to regulate de novo methylation in the germline but does it function in the early embryo? Déborah Bourc'his and colleagues have been investigating this question and, on p. , they report that, although mouse embryos initially contain a maternal store of Dnmt3L, the protein is rapidly degraded. The researchers show that zygotic Dnmt3L deficiency slows down the rate of de novo methylation in the embryo by affecting methylation density at some, but not all, genomic sequences. Importantly, however, Dnmt3L is not strictly required for de novo methylation in the embryo because methylation patterns are eventually established in its absence, possibly through upregulation of Dnmt3A. De novo methylation can therefore be achieved in vivo without Dnmt3L, which suggests that early mouse embryos are more plastic than the germline in terms of how they acquire de novo methylation patterns.
