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Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
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Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
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Journal Article
Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
2020
Overview
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.
De novo DNA methylation is carried out by DNMT3A and DNMT3B, but the distinct functions of these two enzymes is poorly understood. Here the authors present a comprehensive, genome-wide identification of target sites for de novo DNA methylation by the DNMT3A and DNMT3B in mouse ES cells and embryos, identifying unique de novo DNA methylation target sites for both DNMT3 enzymes.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 49/23
/ 49/91
/ 64/60
/ Ablation
/ Animals
/ Cell Differentiation - genetics
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ Embryos
/ Enzymes
/ Epigenetic Repression - genetics
/ Female
/ Genes
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Mammals
/ Mice
/ Mouse Embryonic Stem Cells - cytology
/ Mouse Embryonic Stem Cells - metabolism
/ Mutation
/ Science
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