RRC ID 60830
Author Yagi M, Kabata M, Tanaka A, Ukai T, Ohta S, Nakabayashi K, Shimizu M, Hata K, Meissner A, Yamamoto T, Yamada Y.
Title Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development.
Journal 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.
Volume 11(1)
Pages 3199
Published 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
Times Cited 0
Mice RBRC00209 RBRC03730