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  Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development

Yagi, M., Kabata, M., Tanaka, A., Ukai, T., Ohta, S., Nakabayashi, K., et al. (2020). Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development. Nature Communications, 11: 3199. doi:10.1038/s41467-020-16989-w.

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Yagi, Masaki, Author
Kabata, Mio, Author
Tanaka, Akito , Author
Ukai, Tomoyo , Author
Ohta, Sho, Author
Nakabayashi, Kazuhiko , Author
Shimizu, Masahito , Author
Hata, Kenichiro , Author
Meissner, Alexander1, Author              
Yamamoto, Takuya , Author
Yamada, Yasuhiro , Author
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1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              

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 Abstract: De novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.

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Language(s): eng - English
 Dates: 2020-06-022020-06-24
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/s41467-020-16989-w
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 11 Sequence Number: 3199 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723