Nucleic Acids Research, Vol 26, Issue 11 2536-2540, Copyright © 1998 by Oxford University Press
M Okano, S Xie and E Li
We have shown previously that de novo methylation activities persist in
mouse embryonic stem (ES) cells homozygous for a null mutation of Dnmt1
that encodes the major DNA cytosine methyltransferase. In this study, we
have cloned a putative mammalian DNA methyltransferase gene, termed Dnmt2 ,
that is homologous to pmt1 of fission yeast. Different from pmt1 in which
the catalytic Pro-Pro-Cys (PPC) motif is 'mutated' to Pro- Ser-Cys, Dnmt2
contains all the conserved methyltransferase motifs, thus likely encoding a
functional cytosine methyltransferase. However, baculovirus-expressed Dnmt2
protein failed to methylate DNA in vitro . To investigate whether Dnmt2
functions as a DNA methyltransferase in vivo , we inactivated the Dnmt2
gene by targeted deletion of the putative catalytic PPC motif in ES cells.
We showed that endogenous virus was fully methylated in Dnmt2 -deficient
mutant ES cells. Furthermore, newly integrated retrovirus DNA was
methylated de novo in infected mutant ES cells as efficiently as in
wild-type cells. These results indicate that Dnmt2 is not essential for
global de novo or maintenance methylation of DNA in ES cells.
ARTICLES
Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells
Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine,Harvard Medical School, 149, 13th Street, Charlestown, MA 02129, USA.
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