DNA methyltransferase is actively retained in the cytoplasm during early development

The overall DNA methylation level sharply decreases from the zygote to the blastocyst stage despite the presence of high levels of DNA methyltransfera se (Dnmt1). Surprisingly, the enzyme is localized in the cytoplasm of early embryos despite the presence of several functional nuclear localization si gnals. We mapped a region in the NH2-terminal, regulatory domain of Dnmt1 t hat is necessary and sufficient for cytoplasmic retention during early deve lopment. Altogether, our results suggest that Dnmt1 is actively retained in the cytoplasm, which prevents binding to its DNA substrate in the nucleus and thereby contributes to the erasure of gamete-specific epigenetic inform ation during early mammalian development.