DNA methylation of methylation complex genes in relation to stress and genome-wide methylation in mother-newborn dyads
DNA methylation of methylation complex genes in relation to stress and genome-wide methylation in mother-newborn dyads
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DOI：
10.1002/ajpa.23341
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Mulligan, Connie J.
中科院分区：
文献类型：
--
作者：
Clukay, Christopher J.;Hughes, David A.;Mulligan, Connie J.
早期生活压力被认为具有持久的生物学效应，特别是在健康方面。表观遗传修饰，如DNA甲基化，是介导应激生物学效应的一种可能机制。我们以前发现了母亲压力，新生儿出生体重和DNA甲基化的全基因组测量之间的相关性。为了更好地了解应激对健康的影响，我们研究了与甲基化/去甲基化复合体相关的10个基因。材料与方法检测DNA甲基化和甲基化/去甲基化基因的遗传变异。为每个基因构建平均甲基化测量值，并根据访谈和调查数据，除了遗传变异外，还测试了与母亲压力测量值的相关性（慢性应激和战争创伤）、母体静脉和新生儿脐带全基因组平均甲基化（GMM）和出生体重。DNMT 3A，TET 3，MBD 2，和birthweight.ConclusionsThe协会的母亲GMM和母亲甲基化DNMT 1，DNMT 3A，TET 3，MBD 2是一致的，这些基因的作用，在建立，维持和改变全基因组甲基化模式，在某些情况下，在应对压力。DNMT 1产生在DNA复制期间复制甲基化模式的主要酶之一。DNMT 3A和TET 3与响应糖皮质激素的全基因组低甲基化有关。虽然我们不能确定甲基化的基因和全基因组变化的方向性，但我们的研究结果表明，特定甲基化基因的甲基化改变可能是人类对压力的生物反应的分子机制的一部分。
ObjectivesEarly life stress is known to have enduring biological effects, particularly with respect to health. Epigenetic modifications, such as DNA methylation, are a possible mechanism to mediate the biological effect of stress. We previously found correlations between maternal stress, newborn birthweight, and genome-wide measures of DNA methylation. Here we investigate ten genes related to the methylation/demethylation complex in order to better understand the impact of stress on health.Materials and methodsDNA methylation and genetic variants at methylation/demethylation genes were assayed. Mean methylation measures were constructed for each gene and tested, in addition to genetic variants, for association with maternal stress measures based on interview and survey data (chronic stress and war trauma), maternal venous, and newborn cord genome-wide mean methylation (GMM), and birthweight.ResultsAfter cell type correction, we found multiple pairwise associations between war trauma, maternal GMM, maternal methylation at DNMT1, DNMT3A, TET3, and MBD2, and birthweight.ConclusionsThe association of maternal GMM and maternal methylation at DNMT1, DNMT3A, TET3, and MBD2 is consistent with the role of these genes in establishing, maintaining and altering genome-wide methylation patterns, in some cases in response to stress. DNMT1 produces one of the primary enzymes that reproduces methylation patterns during DNA replication. DNMT3A and TET3 have been implicated in genome-wide hypomethylation in response to glucocorticoid hormones. Although we cannot determine the directionality of the genic and genome-wide changes in methylation, our results suggest that altered methylation of specific methylation genes may be part of the molecular mechanism underlying the human biological response to stress.