Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Role of Tet3 and DNA replication in zygotic demethylation of both paternal and maternal genomes [RRBS]

ABSTRACT: With the exception of imprinted genes and certain repeats, DNA methylation is globally erased during pre-implantation development. Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global paternal DNA demethylation, but demethylation of the maternal genome occurs via replication. Here we present genome-scale DNA methylation maps for both the paternal and maternal genomes of Tet3-depleted and/or DNA replication-inhibited zygotes. In both genomes, we found that inhibition of DNA replication blocks DNA demethylation independently from Tet3 function, and that Tet3 facilitates DNA demethylation by coupling with DNA replication. For both, our data indicate that replication-dependent dilution is the major contributor to demethylation, but Tet3 plays an important role, particularly at certain loci. Our study therefore both defines the respective functions of Tet3 and DNA replication in paternal DNA demethylation and reveals an unexpected contribution of Tet3 to demethylation of the maternal genome. In this data set, we include RRBS data of manually isolated paternal and maternal pronuclei from both WT and Tet3 CKO zygotes with or without aphidicolin treatment

ORGANISM(S): Mus musculus

SUBMITTER: Yi Zhang

PROVIDER: E-GEOD-61330 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes.

Shen Li L Inoue Azusa A He Jin J Liu Yuting Y Lu Falong F Zhang Yi Y

Cell stem cell 20141001 4

With the exception of imprinted genes and certain repeats, DNA methylation is globally erased during preimplantation development. Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global paternal DNA demethylation, but demethylation of the maternal genome occurs via replication. Here we present genome-scale DNA methylation maps for both the paternal and maternal genomes of Tet3-depleted and/or DNA replic ...[more]

PMID: 25280220

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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

Role of Tet3 and DNA replication in zygotic demethylation of both paternal and maternal genomes [RRBS]

Publications

Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes.

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