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Title: Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
Authors: Yagi, Masaki
Kabata, Mio
Tanaka, Akito
Ukai, Tomoyo
Ohta, Sho
Nakabayashi, Kazuhiko
Shimizu, Masahito
Hata, Kenichiro
Meissner, Alexander
Yamamoto, Takuya  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-0022-3947 (unconfirmed)
Yamada, Yasuhiro
Author's alias: 八木, 正樹
蒲田, 未央
田中, 彰人
鵜飼, 智代
太田, 翔
中林, 一彦
清水, 雅仁
秦, 健一郎
山本, 拓也
山田, 泰広
Keywords: Differentiation
DNA methylation
Embryonic stem cells
Gene regulation
Issue Date: 24-Jun-2020
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 11
Thesis number: 3199
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.
Description: DNAメチル化酵素DNMT3AおよびDNMT3Bの特異的機能の発見 --哺乳類の発生過程やがん発症のメカニズム解明に貢献--. 京都大学プレスリリース. 2020-07-01.
Rights: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/252378
DOI(Published Version): 10.1038/s41467-020-16989-w
PubMed ID: 32581223
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2020-07-01
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