Maternal vitamin C regulates reprogramming of DNA methylation and germline development

DiTroia, Stephanie; Percharde, Michelle; Guerquin, Marie-Justine; Wall, Estelle A.; Collignon, Evelyne; Ebata, Kevin; Mesh, Kathryn; Mahesula, Swetha; Agathocleous, Michalis; Laird, Diana J.; Livera, Gabriel; Ramalho-Santos, Miguel

doi:10.1038/s41586-019-1536-1

Cited by 80 publications

(70 citation statements)

References 50 publications

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“…Treatment with vitamin C leads to a signi cant increase in the levels of oxidized methylcytosine, consistent with its function in stimulating the catalytic activity of TET enzymes [31][32][33]. Meanwhile, maternal vitamin C de ciency leads to incomplete loss of DNA methylation in the female mice embryonic germline cells presumably through inactivation of TET1 [34]. In addition, the BCAA (branched-chain amino acid) -BCAT1 (BCAA transaminase 1) -αKG (αketoglutarate) axis also engages in TET activity.…”

Section: Discussionmentioning

confidence: 63%

Insufficient gestational weight gain associated with higher DNA methylation in cord blood cells

Kawai¹,

Miyakoshi

Kasuga

et al. 2020

Preprint

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Background Gestational weight gain (GWG) is one of the crucial factors affecting fetal growth as well as the in utero environment, influencing fetal cell programming during development. We reported previously that GWG affected the occurrence of outlying CpG methylation values of placental DNA in a U-shaped manner, with the occurrence of outlying values from adequate GWG subjects positioned at the bottom of the curve. In the present study, we aimed to elucidate the effects of GWG on the infant epigenome by the view that the influence of insufficient GWG on infant DNA methylation may turn in some other direction at the borderline of the optimal weight gain. Method We collected cord blood from 60 subjects with uncomplicated term delivery whose mean pre-pregnancy body mass index and mean GWG was 19.8 ± 1.9 and 8.1 ± 4.3 kg, respectively. Cord blood DNA was underwent analysis using the Infinium MethylationEPIC BeadChip to profile genome-wide methylation status. Results GWG was continuously associated with cord blood DNA methylation at five CpG loci significantly (multiple test corrected p-value, 0.043) in the lower than upper limit of the recommended GWG group (n = 51). The significant association between DNA methylation levels and GWG was disappeared when added 9 subjects who gained weight more than upper limit of recommendation during pregnancy. The methylation plot of the five loci plateaued or traced a U-curve near the border of the upper limit of the GWG recommendation. Cord blood DNA methylation of these five were all negatively associated with GWG. Validation using deep targeted bisulfite sequencing reproduced negative correlations between GWG and methylation levels within one of the five targets; at the upstream of LINC01816 . This region has been annotated as a promoter or an enhancer depending on blood cell types based on their epigenetic marks. Conclusions It is known that demethylation at enhancer region in genome is one of the features during late fetal development. We found that insufficient GWG showed higher methylation status in some enhancer-candidate loci in cord blood cells, which may indicate incomplete demethylation during in utero development.

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Section: Discussionmentioning

confidence: 63%

Insufficient gestational weight gain associated with higher DNA methylation in cord blood cells

Kawai¹,

Miyakoshi

Kasuga

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…DOHaD involves abnormal fetal growth and developmental disorders, which are not affected by genetic abnormalities but by epigenetic changes influenced by maternal and paternal nutritional status or stress during pregnancy or gametogenesis [76]. Thus, it has been reported that maternal vitamin C deficiency does not affect embryonic development but is known to cause a reduction in the number of germ cells in the fetus and reduced fertility in adulthood [77]. As for paternal effect, it has also been reported that children whose fathers consumed a diet rich in methyl-donor molecules have altered cognitive and neurological functions [78].…”

Section: Discussionmentioning

confidence: 99%

Editing DNA Methylation in Mammalian Embryos

Yamazaki

Hatano

Taniguchi

et al. 2020

IJMS

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DNA methylation in mammals is essential for numerous biological functions, such as ensuring chromosomal stability, genomic imprinting, and X-chromosome inactivation through transcriptional regulation. Gene knockout of DNA methyltransferases and demethylation enzymes has made significant contributions to analyzing the functions of DNA methylation in development. By applying epigenome editing, it is now possible to manipulate DNA methylation in specific genomic regions and to understand the functions of these modifications. In this review, we first describe recent DNA methylation editing technology. We then focused on changes in DNA methylation status during mammalian gametogenesis and preimplantation development, and have discussed the implications of applying this technology to early embryos.

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“…TEs such as LINE1 and various ERVs become globally demethylated and expressed during the major waves of epigenetic erasure that take place during preimplantation and germline development ( Figure 1 ). Similarly, a relaxation of H3K9me2‐based repression of TEs occurs in PGCs, contributing to their derepression . As described above, many TE families act as important cis ‐elements for gene regulation.…”

Section: Emerging Evidence For Essential Roles For Expressed Tes Durimentioning

confidence: 92%

“…For example, subnutrition during gestation leads to higher incidence of metabolic, cardiovascular and neurological disorders in adulthood . Recent studies have begun to reveal potential molecular mechanisms of how environmental perturbations during pregnancy can impact the fetus . Interestingly, these molecular mechanisms of environment–embryo communication involve epigenetic layers of gene regulation known to impact directly the expression of TEs, such as DNA methylation .…”

Section: Stress Tes and Evolvabilitymentioning

confidence: 99%

What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

2020

Self Cite

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Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis‐elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.

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Maternal vitamin C regulates reprogramming of DNA methylation and germline development

Cited by 80 publications

References 50 publications

Insufficient gestational weight gain associated with higher DNA methylation in cord blood cells

Insufficient gestational weight gain associated with higher DNA methylation in cord blood cells

Editing DNA Methylation in Mammalian Embryos

What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

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