Dataset Information

Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development

ABSTRACT: In mammals, DNA 5-hydroxymethylcytosine (5hmC) is involved in methylation reprogramming during early embryonic development. Yet, to what extent 5hmC participates in genome-wide methylation reprogramming remains largely unknown. Here, we characterize the 5hmC landscapes in mouse early embryos and germ cells with parental allele specificity. DNA hydroxymethylation was most strongly correlated with DNA demethylation as compared with de novo or maintenance methylation in zygotes, while 5hmC was targeted to particular de novo methylated sites in postimplantation epiblasts. Surprisingly, DNA replication was also required for 5hmC generation, especially in the female pronucleus. More strikingly, aberrant nuclear localization of Dnmt1/Uhrf1 in mouse zygotes due to maternal deficiency of Nlrp14 led to defects in DNA-replication-coupled passive demethylation and impaired 5hmC deposition, revealing the divergency between genome-wide 5-methylcytosine (5mC) maintenance and Tet-mediated oxidation. In summary, our work provides insights and a valuable resource for the study of epigenetic regulation in early embryo development.

ORGANISM(S): Mus musculus

PROVIDER: GSE186357 | GEO | 2022/10/28

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Fertilization triggers a global erasure of 5-methylcytosine from paternal DNA as part of extensive epigenetic reprogramming during the transition from gametic specialization to totipotency. This active removal has been shown to involve oxidation by TET3, but the targeting of this pathway and the wider context of demethylation remain poorly understood. We optimized a novel technique for whole-genome bisulfite sequencing and applied it to wild-type and TET3-deficient zygotes, using SNPs to access paternal alleles. As the great majority of sperm-contributed methylation lies outside the CpG islands (CGIs) and promoters analysed to date, these genome-wide methylation profiles allow paternal methylation trajectories in the zygote to be comprehensively examined for the first time. This global view revealed that in addition to pervasive loss of methylation from intergenic sequences and most repetitive elements, gene bodies constitute a major target of zygotic demethylation. Methylation loss is associated with zygotic genome activation, and at gene bodies is also linked to increased transcriptional noise in the early embryo. Our data maps the primary contribution of oxidative demethylation to a subset of gene bodies and single-copy intergenic sequences, and implicates the action of redundant pathways at many loci. We further uncover a novel function for TET3 in protection from de novo methylation at CGIs and promoters. This work adds new breadth to our understanding of the molecular events involved in reprogramming gametic identity following fertilization. Three independent collections of zygotes were performed for each genotype (control and TET3 deletion), giving a total of 225 control and 237 TET3 deletion zygotes, of which 120 and 129 were derived from 129S2/SvHsd studs for control and TET3 samples, respectively. Zygotes were pooled and whole-genome bisulfite libraries were prepared using a post-bisulfite adaptor tagging strategy optimized from (Miura et al. Nucleic Acids Research 2012, 40:e136)

Dataset Information

Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets