| RRC ID |
60830
|
| 著者 |
Yagi M, Kabata M, Tanaka A, Ukai T, Ohta S, Nakabayashi K, Shimizu M, Hata K, Meissner A, Yamamoto T, Yamada Y.
|
| タイトル |
Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
11(1)
|
| ページ |
3199
|
| 公開日 |
2020-6-24
|
| DOI |
10.1038/s41467-020-16989-w
|
| PII |
10.1038/s41467-020-16989-w
|
| PMID |
32581223
|
| PMC |
PMC7314859
|
| MeSH |
Animals
Cell Differentiation / genetics
Cells, Cultured
DNA (Cytosine-5-)-Methyltransferases / genetics
DNA (Cytosine-5-)-Methyltransferases / metabolism*
DNA Methylation*
DNA Methyltransferase 3A
Epigenetic Repression / genetics
Female
Humans
Mice
Mouse Embryonic Stem Cells / cytology
Mouse Embryonic Stem Cells / metabolism
Mutation
Organ Specificity
Polycomb-Group Proteins
Transcription Initiation Site
|
| IF |
11.878
|
| 引用数 |
0
|
| リソース情報 |
| 実験動物マウス |
RBRC00209
RBRC03730 |
