TY  - JOUR
A1  - Hattori, Naka
A1  - Abe, Tetsuya
A1  - Hattori, Naoko
A1  - Suzuki, Masako
A1  - Matsuyama, Tomoki
A1  - Yoshida, Shigeo
A1  - Li, En
A1  - Shiota, Kunio
T1  - Preference of DNA Methyltransferases for CpG Islands in Mouse Embryonic Stem Cells
Y1  - 2004/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1733 
EP  - 1740 
DO  - 10.1101/gr.2431504 
VL  - 14 
IS  - 9 
UR  - http://genome.cshlp.org/content/14/9/1733.abstract 
N2  - Many CpG islands have tissue-dependent and differentially methylated regions (T-DMRs) in normal cells and tissues. To elucidate how DNA methyltransferases (Dnmts) participate in methylation of the genomic components, we investigated the genome-wide DNA methylation pattern of the T-DMRs with Dnmt1-, Dnmt3a-, and/or Dnmt3b-deficient ES cells by restriction landmark genomic scanning (RLGS). Approximately 1300 spots were detected in wild-type ES cells. In Dnmt1-/- ES cells, additional 236 spots emerged, indicating that the corresponding loci are methylated by Dnmt1 in wild-type ES cells. Intriguingly, in Dnmt3a-/-Dnmt3b-/- ES cells, the same 236 spots also emerged, and no additional spots appeared differentially. Therefore, Dnmt1 and Dnmt3a/3b share targets in CpG islands. Cloning and virtual image RLGS revealed that 81% of the RLGS spots were associated with genes, and 62% of the loci were in CpG islands. By contrast to the previous reports that demethylation at repeated sequences was severe in Dnmt1-/- cells compared with Dnmt3a-/-Dnmt3b-/- cells, a complete loss of methylation was observed at RLGS loci in Dnmt3a-/-Dnmt3b-/- cells, whereas methylation levels only decreased to 16% to 48% in the Dnmt1-/- cells. We concluded that there are CpG islands with T-DMR as targets shared by Dnmt1 and Dnmt3a/3b and that each Dnmt has target preferences depending on the genomic components. 
ER  -