A short DNA methyltransferase isoform restores methylation in vivo

Item Type:	Article
Title:	A short DNA methyltransferase isoform restores methylation in vivo
Creators Name:	Gaudet, F. and Talbot, D. and Leonhardt, H. and Jaenisch, R.
Abstract:	Two murine DNA methyltransferase isoforms (MTases) have been observed, a longer form in somatic and embryonic stem (ES) cells and a shorter form in oocytes and preimplantation embryos. While the longer MTase is associated with maintenance methyltransferase activity in replicating cells, little is known about the shorter form. We present genetic and biochemical evidence that both isoforms are expressed from the same Dnmt1 gene by using different translation initiation sites in exons 1 and 4. We further demonstrate that the shorter isoform can functionally rescue Dnmt1 null ES cells that have a hypomethylated genome. These rescued ES cells differentiate in vivo into a variety of cell types, unlike the Dnmt1 null ES cells that die upon induction of differentiation. These results show that the shorter isoform can substitute for the longer maintenance MTase in ES and differentiated cells. Our data further indicate that the shorter MTase isoform found in oocytes is fully functional in vivo and may play an active role in the regulation of DNA methylation and the establishment of imprinting patterns.
Keywords:	Amino Acid Sequence, Base Sequence, Cell Differentiation, Cultured Cells, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, DNA Primers, Isoenzymes, Mammalian Embryo, Molecular Sequence Data, Protein Biosynthesis, Site-Directed Mutagenesis, Stem Cells, Animals, Mice
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	273
Number:	49
Page Range:	32725-32729
Date:	4 December 1998
Official Publication:	https://doi.org/10.1074/jbc.273.49.32725
PubMed:	View item in PubMed

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