Oocyte age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886).
Oocyte age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886).
复制标题
卵母细胞年龄和孕前饮酒与非编码RNA（nc886）的表观遗传印记高度相关。
DOI：
10.1073/pnas.2026580118
复制
发表时间：
2021-03-23
影响因子：
11.1
通讯作者：
Jones PA
中科院分区：
文献类型：
--
作者：
Carpenter BL;Remba TK;Thomas SL;Madaj Z;Brink L;Tiedemann RL;Odendaal HJ;Jones PA
基因组印记对人类发育至关重要，在受精前发生在生殖细胞中。非编码RNA nc886是已知的100多个这样的人类基因中唯一一个显示母体印记频率不同的例子。在这里，我们表明DNA甲基化印记存在于卵母细胞中，并且印记的概率随着母亲年龄的增加而增加。重要的是，我们证明了饮酒而不是吸烟与较低的印记频率有关。虽然大多数研究都集中在受孕后的发育时间上，但我们的工作表明，母亲的年龄和怀孕前一年的暴露可能会改变表观基因组，从而改变发育中的孩子。基因组印记发生在受精之前，影响发育中的孩子的每一个细胞，可能对环境扰动很敏感。非编码核糖核酸nc886(也称为VTRNA2-1)是已知的唯一通过∼甲基化印记的DNA100人类基因，显示出种群中的多态印记。NC886基因是∼1.6kb差异甲基化区域的一部分，该区域在卵母细胞中甲基化，并在全球约75%的人类中沉默于母体等位基因。在这里，我们证明了个体在nc886DMR有无印记在不同的组织中是一致的，证实了印记是在细胞分化之前建立的，并保持到成年。我们调查了来自南非的1100多对母子，研究了新生儿的印记频率与母亲年龄、怀孕前饮酒和吸烟之间的关系。在年龄较大的母亲中，新生儿印记的可能性增加，而在怀孕前饮酒的母亲中，印记的可能性降低。另一方面，吸烟与印记的频率没有明显的关系。这些数据显示了卵母细胞成熟过程中的表观遗传学变化，这可能会受到环境的影响。人们一直关注避免在怀孕期间饮酒，但我们的数据表明，怀孕前饮酒可能会影响新生儿的表观基因组。
Genomic imprinting is essential for human development and occurs in germ cells before fertilization. The noncoding RNA, nc886, is the only known example of more than 100 such human genes which shows variable frequencies of maternal imprinting. Here, we show that the DNA methylation imprint is present in oocytes and that the probability of imprinting increases as a function of maternal age. Importantly, we demonstrate that alcohol consumption but not cigarette smoking is associated with a lower frequency of imprinting. While most studies focus on the postconceptional developmental time, our work indicates that maternal age and exposures the year prior to pregnancy may alter the epigenome and therefore the developing child. Genomic imprinting occurs before fertilization, impacts every cell of the developing child, and may be sensitive to environmental perturbations. The noncoding RNA, nc886 (also called VTRNA2-1) is the only known example of the ∼100 human genes imprinted by DNA methylation, that shows polymorphic imprinting in the population. The nc886 gene is part of an ∼1.6-kb differentially methylated region (DMR) that is methylated in the oocyte and silenced on the maternal allele in about 75% of humans worldwide. Here, we show that the presence or absence of imprinting at the nc886 DMR in an individual is consistent across different tissues, confirming that the imprint is established before cellular differentiation and is maintained into adulthood. We investigated the relationships between the frequency of imprinting in newborns and maternal age, alcohol consumption and cigarette smoking before conception in more than 1,100 mother/child pairs from South Africa. The probability of imprinting in newborns was increased in older mothers and decreased in mothers who drank alcohol before conception. On the other hand, cigarette smoking had no apparent relationship with the frequency of imprinting. These data show an epigenetic change during oocyte maturation which is potentially subject to environmental influence. Much focus has been placed on avoiding alcohol consumption during pregnancy, but our data suggest that drinking before conception may affect the epigenome of the newborn.
登录
查看更多内容
DOI：
10.1073/pnas.1815005115
发表时间：
2018-12-18
影响因子：
11.1
作者：
Carpenter BL;Zhou W;Madaj Z;DeWitt AK;Ross JP;Grønbæk K;Liang G;Clark SJ;Molloy PL;Jones PA
通讯作者：
Jones PA
影响因子：
12.3
作者：
Lokk K;Modhukur V;Rajashekar B;Märtens K;Mägi R;Kolde R;Koltšina M;Nilsson TK;Vilo J;Salumets A;Tõnisson N
通讯作者：
Tõnisson N
影响因子：
4.5
作者：
Calderon, Brenda M.;Conn, Graeme L.
通讯作者：
Conn, Graeme L.
影响因子：
2.8
作者：
Dukes, Kimberly A.;Burd, Larry;Kinney, Hannah C.
通讯作者：
Kinney, Hannah C.
影响因子：
2.3
作者：
Dukes, Kimberly;Tripp, Tara;Burd, Larry
通讯作者：
Burd, Larry