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 journalArticle

67 Citations (Scopus)

Abstract

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
Volume14
Issue number9
DOIs
StatePublished - Sep 2004
Externally publishedYes

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CpG Islands
Methyltransferases
DNA
Methylation
Genome Components
Mouse Embryonic Stem Cells
DNA Methylation
Organism Cloning

ASJC Scopus subject areas

  • Genetics

Cite this

Hattori, N., Abe, T., Hattori, N., Suzuki, M., Matsuyama, T., Yoshida, S., ... Shiota, K. (2004). Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells. Genome Research, 14(9), 1733-1740. https://doi.org/10.1101/gr.2431504

Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells. / Hattori, Naka; Abe, Tetsuya; Hattori, Naoko; Suzuki, Masako; Matsuyama, Tomoki; Yoshida, Shigeo; Li, En; Shiota, Kunio.

In: Genome Research, Vol. 14, No. 9, 09.2004, p. 1733-1740.

Research output: Contribution to journalArticle

Hattori, N, Abe, T, Hattori, N, Suzuki, M, Matsuyama, T, Yoshida, S, Li, E & Shiota, K 2004, 'Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells', Genome Research, vol. 14, no. 9, pp. 1733-1740. https://doi.org/10.1101/gr.2431504
Hattori, Naka ; Abe, Tetsuya ; Hattori, Naoko ; Suzuki, Masako ; Matsuyama, Tomoki ; Yoshida, Shigeo ; Li, En ; Shiota, Kunio. / Preference of DNA methyltransferases for CpG islands in mouse embryonic stem cells. In: Genome Research. 2004 ; Vol. 14, No. 9. pp. 1733-1740.
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