The regulation of gene expression during development often involves epigenetic changes. In vertebrates, for example, the cytosine methyltransferase Dnmt1 is essential for gene silencing in early embryos. It is widely thought that Dnmt1 fulfils this role by maintaining DNA methylation at inactive genes. However, on , Richard Meehan and colleagues challenge this dogma by showing that xDnmt1 regulates gene silencing in early Xenopus embryos independently of its DNA methyltransferase activity. The researchers show that a partial reduction of xDnmt1 protein levels by morpholinos prematurely activates zygotic gene expression before the pre-midblastula transition, when these genes are normally activated in Xenopus embryos. However, this premature gene activation occurs without any decrease in DNA methylation, either globally or at specific loci. Furthermore, the injection of an mRNA encoding a catalytically inactive form of human DNMT1 rescues the morpholino-treated embryos. These and other data suggest that xDnmt1 (and possibly mammalian Dnmt1) regulates embryonic gene silencing both through its catalytic activity and by acting as a direct, non-catalytic transcription repressor protein.
