Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells

Naka Hattori, Tetsuya Abe, Naoko Hattori, Masako Suzuki, Tomoki Matsuyama, Shigeo Yoshida, En Li, Kunio Shiota

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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 visual image RLGS revealed that 81% of the RLGS spas 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.

Original languageEnglish (US)
Pages (from-to)1733-1740
Number of pages8
JournalGenome research
Issue number9
StatePublished - Sep 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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