Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos

Although DNA methylation is a relative-ly stable epigenetic modification, globalDNA demethylation has been observed in two stages during embryogenesis. One takes place in zygotes, when the paternal genome is preferentially demethylated (1). Despite great ef-forts in identifying the responsible enzymes, the identity of the putative DNA demethylase has re-mained elusive (2). Recent demonstration that the Tet (ten eleven translocation) family proteins are capable of converting 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC) raises the possibility that Tet proteins might be involved in this process (3, 4). To address this possibility, we performed im-munostaining that demonstrated, similar to recently published results (5, 6), that loss of 5mC staining i