Maternal vitamin C regulates reprogramming of DNA methylation and germline development.
Maternal vitamin C regulates reprogramming of DNA methylation and germline development.
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DOI：
10.1038/s41586-019-1536-1
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发表时间：
2019-09
期刊：
影响因子：
64.8
通讯作者：
Ramalho-Santos M
中科院分区：
文献类型：
--
作者：
DiTroia SP;Percharde M;Guerquin MJ;Wall E;Collignon E;Ebata KT;Mesh K;Mahesula S;Agathocleous M;Laird DJ;Livera G;Ramalho-Santos M
人们通常认为发育是基因组中固有的，但一些证据表明，它很容易受到环境调节的影响，并产生潜在的长期后果，包括哺乳动物。由于具有代际表观遗传效应的潜力，胚胎种系特别令人感兴趣。哺乳动物种系经历广泛的 DNA 去甲基化，这在很大程度上是由于连续细胞分裂过程中的被动稀释而发生的，同时还伴随着通过 10-11 易位 (Tet) 酶进行的主动 DNA 去甲基化。 Tet 活性已被证明受到营养物质和代谢物的调节，包括维生素 C (VitC)。我们在此报告，在小鼠模型中，母体 VitC 是 DNA 适当去甲基化和雌性胎儿生殖细胞发育所必需的。母体 VitC 缺乏不会影响整体胚胎发育，但会导致生殖细胞数量减少、减数分裂延迟和成年期生育力降低。来自 VitC 缺陷胚胎的生殖细胞的转录组与携带 Tet1 无效突变的胚胎的转录组非常相似。 VitC 缺乏会导致 DNA 甲基化谱异常，其中包括减数分裂和转座元件关键调节因子的不完全去甲基化。这些发现表明，妊娠期间 VitC 的缺乏部分重现了 Tet1 的损失，并为根据环境条件调整繁殖力提供了潜在的代际机制。
Development is often assumed to be hardwired in the genome, but several lines of evidence indicate that it is susceptible to environmental modulation with potential long-term consequences, including in mammals. The embryonic germline is of particular interest because of the potential for intergenerational epigenetic effects. The mammalian germline undergoes extensive DNA demethylation that occurs in large part by passive dilution over successive cell divisions, accompanied by active DNA demethylation via Ten-eleven translocation (Tet) enzymes. Tet activity has been shown to be modulated by nutrients and metabolites, including Vitamin C (VitC). We report here that maternal VitC is required for proper DNA demethylation and development of female fetal germ cells in a mouse model. Maternal VitC deficiency does not affect overall embryonic development but leads to reduced germ cell numbers, delayed meiosis and reduced fecundity in adulthood. The transcriptome of germ cells from VitC-deficient embryos is remarkably similar to that of embryos carrying a null mutation in Tet1. VitC 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 VitC during gestation partially recapitulates Tet1 loss and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Gkountela S;Zhang KX;Shafiq TA;Liao WW;Hargan-Calvopiña J;Chen PY;Clark AT
通讯作者：
Clark AT