Dnmt1 binds and represses genomic retroelements via DNA methylation in mouse early embryos.
Animals
CpG Islands
/ genetics
DNA (Cytosine-5-)-Methyltransferase 1
/ genetics
DNA Methylation
/ genetics
DNA-Binding Proteins
/ genetics
Embryo, Mammalian
Embryonic Development
/ genetics
Gene Expression Profiling
Genome
/ genetics
Genomic Imprinting
/ genetics
Genomics
Mice
Retroelements
/ genetics
Transcription Factors
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
accepted:
03
07
2020
revised:
10
06
2020
received:
10
05
2019
pubmed:
16
7
2020
medline:
21
10
2020
entrez:
16
7
2020
Statut:
ppublish
Résumé
Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidences of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA adenine methylase identification method, we identified Dnmt1-binding regions in four- and eight-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refutes the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the LINE1 (long interspersed nuclear elements) and ERVK (endogenous retrovirus type K) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.
Identifiants
pubmed: 32667642
pii: 5871879
doi: 10.1093/nar/gkaa584
pmc: PMC7470951
doi:
Substances chimiques
DNA-Binding Proteins
0
Retroelements
0
Transcription Factors
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
Dnmt1 protein, mouse
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
8431-8444Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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