TITLE:
Distinct functions of Dnmt3a and Dnmt3b de novo DNA methyltransferases in ES cell proliferation and differentiation
AUTHORS:
Yoshie Umehara, Kazunori Hanaoka, Daisuke Watanabe
KEYWORDS:
DNA Methylation; Dnmt3a; Dnmt3b; Stem Cells; ES Cells; Differentiation; Ploliferation
JOURNAL NAME:
Stem Cell Discovery,
Vol.3 No.2,
April
23,
2013
ABSTRACT: Two de novo DNA methyltransferases, Dnmt3a and Dnmt3b, have been identified in humans and mice
to contribute to the methylation of unmodified DNA. We recently showed a transition
of de novo DNA methyltransferase expression from Dnmt3b to Dnmt3a during mouse embryogenesis and in
tissue-specific stem cells, suggesting distinct functions of Dnmt3a and Dnmt3b during these processes. In
this study, to characterize the functions of Dnmt3a and Dnmt3b in pluripotent stem cells, we exogenously
transfected ES cells with Dnmt3a
and Dnmt3b cDNAs linked to an internal ribosome entry site-green fluorescent
protein gene, and then analyzed the effects of expression of these de novo DNA
methyltransferases on ES cell growth and differentiation. ES cells expressing
Dnmt3b showed specific downregulation of pluripotency marker genes such as
Nanog and Oct 3/4. In addition, Dnmt3a-transfected
ES cells showed a specific increase in mitotic index, while Dnmt3b-transfected
ES cells showed a decrease in mitotic index. These results suggest that Dnmt3b
has important physiological roles in the initial process of stem cell
differentiation and that Dnmt3a
has a function in stem cell proliferation.