Preference of DNA Methyltransferases for CpG Islands in Mouse Embryonic Stem Cells

Overview

Journal Genome Res

Specialty Genetics

Date 2004 Aug 18

PMID 15310660

Citations 18

Authors

Naka Hattori

Tetsuya Abe

Naoko Hattori

Masako Suzuki

Tomoki Matsuyama

Shigeo Yoshida

En Li

Kunio Shiota

Affiliations

Soon will be listed here.

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 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.

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