Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development.
Animals
Cell Differentiation
/ genetics
Cells, Cultured
DNA (Cytosine-5-)-Methyltransferases
/ genetics
DNA Methylation
DNA Methyltransferase 3A
Epigenetic Repression
/ genetics
Female
Humans
Mice
Mouse Embryonic Stem Cells
/ cytology
Mutation
Organ Specificity
Polycomb-Group Proteins
Transcription Initiation Site
DNA Methyltransferase 3B
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
01
08
2019
accepted:
02
06
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
28
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32581223
doi: 10.1038/s41467-020-16989-w
pii: 10.1038/s41467-020-16989-w
pmc: PMC7314859
doi:
Substances chimiques
DNMT3A protein, human
0
Dnmt3a protein, mouse
0
Polycomb-Group Proteins
0
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
DNA Methyltransferase 3A
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3199Références
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