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Whole genome bisulfite sequencing (WGBS) and RNA-sequencing of preadipocytes from iWAT

ABSTRACT: C57BL/6J male mice received a high-fat diet. DNA methylation profiles by WGBS of preadipocytes from iWAT of Tet3 f/f and Pdgfra-Tet3 KO mice. Expression profiling by RNA-sequencing of preadipocytes from iWAT of Tet3 f/f and Pdgfra-Tet3 KO mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE214483 | GEO | 2023/10/03

REPOSITORIES: GEO

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Haploinsufficiency, but not defective paternal 5mC oxidation, accounts for the developmental defects of maternal Tet3 knockouts

Project description:DNA demethylation of paternal genome in zygotes takes place in various mammals including mice and human. Recent studies have revealed that this is achieved through Tet3-mediated iterative oxidation of 5-methylcytosine (5mC) coupled with replication-dependent dilution. Tet3-mediated paternal DNA demethylation is believed to be required for mouse development given that Tet3 heterozygous embryos, derived by fertilizing Tet3 knockout (KO) oocytes with wild-type (WT) sperms, exhibit 5mC oxidation defects and embryonic sublethality, Here we demonstrate that the sublethality phenotype of the maternal KO mice is caused by haploinsufficiency of Tet3, but not by defective paternal 5mC oxidation. We found that Tet3 heterozygous mice derived from crosses of heterozygous father or mother with WT mice also exhibit sublethality phenotype similarly to Tet3 maternal KO mice. Importantly, embryos reconstituted with WT paternal nuclei that bypassed 5mC oxidation develop to term and grow to adulthood normally. Genome-scale DNA methylation analysis of the maternal KO zygotes and blastocysts demonstrated that hypermethylation caused by the depletion of maternal Tet3 is largely diminished by the blastocyst stage. Our study thus not only demonstrates that Tet3-mediated paternal 5mC oxidation is dispensable for mouse development but also suggests the existence of a compensation mechanism in preimplantation embryos that can compensate for the defective 5mC oxidation in zygotes. This data set includes RRBS data of wild-type and maternal Tet3 KO zygotes and blastocysts (C57BL/6J x CAST/EiJ)

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