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维生素C调控生殖细胞发育
2019-09-05 15:59

美国加州大学旧金山分校的Miguel Ramalho-Santos研究组近期发现,母体维生素C调节DNA甲基化和生殖细胞发育的重编程。该研究2019年9月4日在线发表于《自然》。

通常认为,发育是严格受基因组调控的。但有一些证据表明,发育容易受环境调节的影响,并产生潜在的长期后果,哺乳动物也是如此。由于具有代间表观遗传效应的可能性,生殖细胞特别令人感兴趣。哺乳动物生殖细胞经历广泛的DNA去甲基化,其大部分通过连续细胞分裂的甲基化被动稀释而实现,同时伴随着TET酶的主动DNA去甲基化。已有证据显示TET活性受营养元素和代谢物的调节,如维生素C。

研究人员发现母体维生素C对于小鼠模型中恰当的DNA去甲基化和雌性胎儿生殖细胞发育是必需的。母体维生素C缺乏不影响整体胚胎发育,但导致生殖细胞数量减少、减数分裂延迟和成年后代的生殖力降低。维生素C缺乏胚胎的生殖细胞转录组与Tet1中携带无效突变的胚胎的转录组非常相似。维生素C缺乏导致异常的DNA甲基化谱,包括减数分裂和转座因子的关键调节因子的不完全去甲基化。这些研究结果表明,妊娠期间维生素C缺乏一定程度上类似于TET1的丢失,并为生殖能力适应环境条件提供了潜在代间机制。

附:英文原文

Title: Maternal vitamin C regulates reprogramming of DNA methylation and germline development

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

Issue&Volume: 2019-09-04

Abstract: 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 of methylation over successive cell divisions, accompanied by active DNA demethylation by TET enzymes. TET activity has been shown to be modulated by nutrients and metabolites, such as vitamin C. Here we show that maternal vitamin C is required for proper DNA demethylation and the development of female fetal germ cells in a mouse model. Maternal vitamin C deficiency does not affect overall embryonic development but leads to reduced numbers of germ cells, delayed meiosis and reduced fecundity in adult offspring. The transcriptome of germ cells from vitamin-C-deficient embryos is remarkably similar to that of embryos carrying a null mutation in Tet1. 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 partially recapitulates loss of TET1, and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions.

DOI: 10.1038/s41586-019-1536-1

Source:https://www.nature.com/articles/s41586-019-1536-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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