RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2004 
FD September 01 
VO 14 
IS 9 
SP 1733 
OP 1740 
DO 10.1101/gr.2431504 
UL http://genome.cshlp.org/content/14/9/1733.abstract 
AB 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.