Maternal Vitamin C regulates DNA demethylation and development of the mouse embryonic germline [RNA-Seq]
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PROVIDER: PRJNA431945 | ENA |
REPOSITORIES: ENA
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Project description:Maternal Vitamin C is required in vivo for proper DNA demethylation and development of fetal germ cells in a mouse model of Vitamin C deficiency. Withdrawal of Vitamin C from the maternal diet does not affect overall embryonic development but leads to defects in the fetal germline, which persist well after Vitamin C re-supply during late gestation. The transcriptome of germ cells from Vitamin C-deficient embryos is remarkably similar to that of embryos carrying a mutation in Tet1, which is responsible for DNA demethylation and activation of regulators of meiosis. In agreement with these results, Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in Vitamin C during gestation recapitulates a mutation in Tet1 and disrupts germline reprogramming and development. Our work further indicate that the embryonic germline is sensitive to perturbations of the maternal diet, providing a potential intergenerational mechanism for adjusting fecundity to environmental quality.
2019-07-01 | GSE109746 | GEO
Project description:Maternal Vitamin C is required in vivo for proper DNA demethylation and development of fetal germ cells in a mouse model of Vitamin C deficiency. Withdrawal of Vitamin C from the maternal diet does not affect overall embryonic development but leads to defects in the fetal germline, which persist well after Vitamin C re-supply during late gestation. The transcriptome of germ cells from Vitamin C-deficient embryos is remarkably similar to that of embryos carrying a mutation in Tet1, which is responsible for DNA demethylation and activation of regulators of meiosis. In agreement with these results, Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in Vitamin C during gestation recapitulates a mutation in Tet1 and disrupts germline reprogramming and development. Our work further indicate that the embryonic germline is sensitive to perturbations of the maternal diet, providing a potential intergenerational mechanism for adjusting fecundity to environmental quality.
2019-07-01 | GSE109745 | GEO
Project description:Maternal Vitamin C is required in vivo for proper DNA demethylation and development of fetal germ cells in a mouse model of Vitamin C deficiency. Withdrawal of Vitamin C from the maternal diet does not affect overall embryonic development but leads to defects in the fetal germline, which persist well after Vitamin C re-supply during late gestation. The transcriptome of germ cells from Vitamin C-deficient embryos is remarkably similar to that of embryos carrying a mutation in Tet1, which is responsible for DNA demethylation and activation of regulators of meiosis. In agreement with these results, Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in Vitamin C during gestation recapitulates a mutation in Tet1 and disrupts germline reprogramming and development. Our work further indicate that the embryonic germline is sensitive to perturbations of the maternal diet, providing a potential intergenerational mechanism for adjusting fecundity to environmental quality.
2019-07-01 | GSE125496 | GEO
Project description:Maternal Vitamin C is required in vivo for proper DNA demethylation and development of fetal germ cells in a mouse model of Vitamin C deficiency. Withdrawal of Vitamin C from the maternal diet does not affect overall embryonic development but leads to defects in the fetal germline, which persist well after Vitamin C re-supply during late gestation. The transcriptome of germ cells from Vitamin C-deficient embryos is remarkably similar to that of embryos carrying a mutation in Tet1, which is responsible for DNA demethylation and activation of regulators of meiosis. In agreement with these results, Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in Vitamin C during gestation recapitulates a mutation in Tet1 and disrupts germline reprogramming and development. Our work further indicate that the embryonic germline is sensitive to perturbations of the maternal diet, providing a potential intergenerational mechanism for adjusting fecundity to environmental quality.
2019-07-01 | GSE125495 | GEO
Project description:Maternal Vitamin C regulates DNA demethylation and development of the mouse embryonic germline
| PRJNA431912 | ENA
Project description:Maternal Vitamin C regulates DNA demethylation and development of the mouse embryonic germline [RRBS]
| PRJNA431944 | ENA
Project description:Maternal Vitamin C regulates DNA demethylation and devlopment of the mouse embryonic germline [Cut&Run]
| PRJNA516596 | ENA
Project description:Maternal Vitamin C regulates DNA demethylation and devlopment of the mouse embryonic germline [soma RNA-seq]
| PRJNA516595 | ENA
Project description:Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in ES cells. Vitamin C treatment reduces global levels of H3K9me2, but not other histone methylation marks analyzed, as measured by Western blot, immunofluorescence and mass spectrometry. Vitamin C leads to widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 hours and is reversible. Importantly, we found that the histone demethylases Kdm3a and Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet-mediated DNA demethylation are independent processes. Lastly, we document Kdm3a/b are partially required for the up-regulation of germline genes by vitamin C. These results reveal a specific role for vitamin C in histone demethylation in ES cells, and document that DNA methylation and H3K9me2 cooperate to silence germline genes in pluripotent cells.
2017-06-30 | GSE84009 | GEO
Project description:DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germline and may be mediated by Tet (ten-eleven-translocation) enzymes, which convert 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Tet enzymes have been extensively studied in mouse embryonic stem (ES) cells, which are generally cultured in the absence of Vitamin C, a potential co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like Tets. Here we report that addition of Vitamin C to ES cells promotes Tet activity leading to a rapid and global increase in hmC. This is followed by DNA demethylation of numerous gene promoters and up-regulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site (TSS) of genes affected by Vitamin C treatment. Importantly, Vitamin C, but not other antioxidants, enhances the activity of recombinant human Tet1 in a biochemical assay and the Vitamin C-induced changes in hmC and mC are entirely suppressed in Tet1/2 double knockout (Tet DKO) ES cells. Vitamin C has the strongest effects on regions that gain methylation in cultured ES cells compared to blastocysts and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A-particle (IAP) elements, which are resistant to demethylation in the early embryo, are resistant to Vitamin C-induced DNA demethylation. Collectively, this study establishes that Vitamin C is a direct regulator of Tet activity and DNA methylation fidelity in ES cells. Oct4-GiP mouse embryonic stem (ES) cells were cultured in the presence or absence of Vitamin C (L-ascorbic acid 2-phosphate, 200 M-NM-<g/ml) for 72 hours. RNA was harvested from biological triplicates for each condition and hybridized to Affymetrix microarrays. Cells were maintained in N2B27 medium supplemented with LIF (1000 U/ml), MEK inhibitor PD0325901 (1 M-NM-<M), and GSK3M-NM-2 inhibitor CHIR99021 (3 M-NM-<M).
2013-06-30 | E-GEOD-46319 | biostudies-arrayexpress