Laboratories & Administration Office

Laboratory of Epigenetics

member

Director Shoji TAJIMA
准教授 Isao SUETAKE
助教 Hironobu KIMURA
Technical Assistant Chika NISHIO
Junichi MIYAGAWA

連絡先

Tel 81-6-6879-8627
Fax 81-6-6879-8629
E-mail

研究概要

In vertebrates, genomic DNA is often methylated at the 5th position of cytosine in the sequence of CpG. The methyl group is transferred from S-adenosylmethionine by DNA methyltransferase. The DNA methylation in vertebrates functions as a regulatory mechanism for the gene expression. Our final goal is to elucidate the mechanisms how DNA methylation state and the expression of methylated genes are regulated.
The methylation pattern of genomic DNA is dynamic and changes during cell differentiation. DNA methyltransferases Dnmt3a and Dnmt3b are responsible in creating DNA methylation patterns. From the DNA methylation study using reconstituted nucleosomes as substrate, we propose that the preferential DNA methylation activity of Dnmt3a towards the naked part of nucleosomal DNA and the significant methylation activity of Dnmt3b towards the nucleosome core region contribute to their distinct methylation of genomic DNA in vivo. Dnmt3L, which is a family member of Dnmt3 but has no DNA methylation activity, is shown to be indispensable for the global meth-ylation in germ cells. Dnmt3L directly interacts with Dnmt3a and Dnmt3b to facilitate their activity. Dnmt1 maintains the DNA methylation patterns once formed in a processive manner.


<Fig.1>
Schematic illustration of the members of DNA methyltransferase family Dnmts.
Up to present, 4 genes, Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3L, are identified.


<Fig.2>
De novo DNA methylation activity of Dnmt3a and Dnmt3b towards nucleosomes.
Dnmt3b, of which expression is stage- and cell type-specific, can methylate nucleosome
core region, and may contribute to global methylation. Chromatin remodeling that
promotes the creation of naked DNA may regulate Dnmt3a-dependent methylation.

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