Role of Tet3 and DNA replication in zygotic demethylation of both paternal and maternal genomes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61331 | GEO | 2014/10/21
SECONDARY ACCESSION(S): PRJNA260789
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-21 | E-GEOD-61331 | biostudies-arrayexpress
Project description: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
2014-10-21 | E-GEOD-61330 | biostudies-arrayexpress
Project description: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 RNA-Seq data of mouse 2-cell embryos and blastocysts derived from both wildtype and Tet3-null oocytes
2014-10-21 | E-GEOD-61329 | biostudies-arrayexpress
Project description: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.
2014-10-21 | GSE61330 | GEO
Project description: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.
2014-10-21 | GSE61329 | GEO
Project description: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 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 largely by coupling with DNA replication. For both genomes, 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 thus 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.
| S-EPMC4201500 | biostudies-literature
Project description:Role of Tet3 and DNA replication in zygotic demethylation of both paternal and maternal genomes
| PRJNA260789 | ENA
Project description:The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed in early embryogenesis to establish full developmental potential. It is broadly accepted that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes passive demethylation thanks to DNA replication over the subsequent cleavage divisions. Here we reveal that both maternal and paternal genomes undergo widespread active and passive demethylation in the pronuclear zygote before the first mitotic division. Whereas the passive demethylation requires DNA replication, the active demethylation relies on enzymatic oxidation of 5mC, as deletion of the DNA dioxygenase, Tet3, but not the inhibition of replication, blocks the active demethylation. At actively demethylated loci, 5mCs appear to be processed to unmodified cytosines in a manner independent of the DNA glycosylase TDG. These observations suggest the occurrence of genuine active demethylation in both parental genomes following fertilization. An extra supportive Tet3 knock-out female pronuclear sample related to experiment Series GSE56650.
2016-09-01 | E-GEOD-60777 | biostudies-arrayexpress
Project description:The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed in early embryogenesis to establish full developmental potential. It is broadly accepted that the paternal genome is actively demethylated in the zygote while the maternal genome undergoes passive demethylation thanks to DNA replication over the subsequent cleavage divisions. Here we reveal that both maternal and paternal genomes undergo widespread active and passive demethylation in the pronuclear zygote before the first mitotic division. Whereas the passive demethylation requires DNA replication, the active demethylation relies on enzymatic oxidation of 5mC, as deletion of the DNA dioxygenase, Tet3, but not the inhibition of replication, blocks the active demethylation. At actively demethylated loci, 5mCs appear to be processed to unmodified cytosines in a manner independent of the DNA glycosylase TDG. These observations suggest the occurrence of genuine active demethylation in both parental genomes following fertilization.
2016-09-01 | GSE60777 | GEO
Project description:The mechanisms responsible for maintaining genomic methylation imprints in mouse embryos are not understood. We generated a knockout mouse in the Zfp57 locus encoding a KRAB zinc finger protein. Loss of just the zygotic function of Zfp57 causes partial neonatal lethality, whereas eliminating both the maternal and zygotic functions of Zfp57 results in a highly penetrant embryonic lethality. In oocytes, absence of Zfp57 results in failure to establish maternal methylation imprints at the Snrpn imprinted region. Intriguingly, methylation imprints are reacquired specifically at the maternally derived Snrpn imprinted region when the zygotic Zfp57 is present in embryos. This suggests that there may be DNA methylation-independent memory for genomic imprints. Zfp57 is also required for the postfertilization maintenance of maternal and paternal methylation imprints at multiple imprinted domains. The effects on genomic imprinting are consistent with the maternal-zygotic lethality of Zfp57 mutants.
| S-EPMC2593089 | biostudies-literature