Restricted mobility of Dnmt1 in preimplantation embryos: implications for epigenetic reprogramming

Background: Mouse preimplantation development is characterized by both active and passive genomic demethylation. A short isoform of the prevalent maintenance DNA methyltransferase ( DnmtIS) is found in the cytoplasm of preimplantation embryos and transiently enters the nucleus only at the 8- cell stage. Results: Using GFP fusions we show that both the long and short isoforms of DnmtI localize to the nucleus of somatic cells and the cytoplasm of preimplantation embryos and that these subcellular localization properties are independent of phosphorylation. Importantly, photobleaching techniques and salt extraction revealed that DnmtIS has a very restricted mobility in the cytoplasm, while it is highly mobile in the nucleus of preimplantation embryos. Conclusion: The restricted mobility of DnmtIS limits its access to DNA and likely contributes to passive demethylation and epigenetic reprogramming during preimplantationdevelopment.