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© The Rockefeller University Press, 0021-9525/1999/10/25/ $5.00
The Journal of Cell Biology, Volume 147, Number 1, October 4, 1999 25-32

Original Article

DNA Methyltransferase Is Actively Retained in the Cytoplasm during Early Development

M. Cristina Cardosoa and Heinrich Leonhardta
a Max Delbrück Center for Molecular Medicine, Franz Volhard Clinic, 13125 Berlin, Germany

Correspondence to: Heinrich Leonhardt, Franz Volhard Clinic, Wiltbergstrasse 50, 13125 Berlin, Germany. Phone: (30) 9417-2341. Fax:(30) 9417-2336 E-mail:leonhardt{at}fvk-berlin.de.

The overall DNA methylation level sharply decreases from the zygote to the blastocyst stage despite the presence of high levels of DNA methyltransferase (Dnmt1). Surprisingly, the enzyme is localized in the cytoplasm of early embryos despite the presence of several functional nuclear localization signals. We mapped a region in the NH2-terminal, regulatory domain of Dnmt1 that is necessary and sufficient for cytoplasmic retention during early development. 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 information during early mammalian development.

Key Words: cytoplasmic retention, DNA methylation, DNA methyltransferase, genomic imprinting, preimplantation development


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