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Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
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 gene...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314859/ https://www.ncbi.nlm.nih.gov/pubmed/32581223 http://dx.doi.org/10.1038/s41467-020-16989-w |
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author | Yagi, Masaki Kabata, Mio Tanaka, Akito Ukai, Tomoyo Ohta, Sho Nakabayashi, Kazuhiko Shimizu, Masahito Hata, Kenichiro Meissner, Alexander Yamamoto, Takuya Yamada, Yasuhiro |
author_facet | Yagi, Masaki Kabata, Mio Tanaka, Akito Ukai, Tomoyo Ohta, Sho Nakabayashi, Kazuhiko Shimizu, Masahito Hata, Kenichiro Meissner, Alexander Yamamoto, Takuya Yamada, Yasuhiro |
author_sort | Yagi, Masaki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7314859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73148592020-06-26 Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development Yagi, Masaki Kabata, Mio Tanaka, Akito Ukai, Tomoyo Ohta, Sho Nakabayashi, Kazuhiko Shimizu, Masahito Hata, Kenichiro Meissner, Alexander Yamamoto, Takuya Yamada, Yasuhiro Nat Commun Article 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. Nature Publishing Group UK 2020-06-24 /pmc/articles/PMC7314859/ /pubmed/32581223 http://dx.doi.org/10.1038/s41467-020-16989-w Text en © The Author(s) 2020 Open Access 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/. |
spellingShingle | Article Yagi, Masaki Kabata, Mio Tanaka, Akito Ukai, Tomoyo Ohta, Sho Nakabayashi, Kazuhiko Shimizu, Masahito Hata, Kenichiro Meissner, Alexander Yamamoto, Takuya Yamada, Yasuhiro Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title | Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title_full | Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title_fullStr | Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title_full_unstemmed | Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title_short | Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development |
title_sort | identification of distinct loci for de novo dna methylation by dnmt3a and dnmt3b during mammalian development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314859/ https://www.ncbi.nlm.nih.gov/pubmed/32581223 http://dx.doi.org/10.1038/s41467-020-16989-w |
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