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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X
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Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X

机译:慢性社会应激在磷染染患者中诱导DNA甲基化变化

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Chronic stress resulting from prolonged exposure to negative life events increases the risk of mood and anxiety disorders. Although chronic stress can change gene expression relevant for behavior, molecular regulators of this change have not been fully determined. One process that could play a role is DNA methylation, an epigenetic process whereby a methyl group is added onto nucleotides, predominantly cytosine in the CpG context, and which can be induced by chronic stress. It is unknown to what extent chronic social defeat, a model of human social stress, influences DNA methylation patterns across the genome. Our study addressed this question by using a targeted-capture approach called Methyl-Seq to investigate DNA methylation patterns of the dentate gyrus at putative regulatory regions across the mouse genome from mice exposed to 14days of social defeat. Findings were replicated in independent cohorts by bisulfite-pyrosequencing. Two differentially methylated regions (DMRs) were identified. One DMR was located at intron 9 of Drosha, and it showed reduced methylation in stressed mice. This observation replicated in one of two independent cohorts. A second DMR was identified at an intergenic region of chromosome X, and methylation in this region was increased in stressed mice. This methylation difference replicated in two independent cohorts and in Major Depressive Disorder (MDD) postmortem brains. These results highlight a region not previously known to be differentially methylated by chronic social defeat stress and which may be involved in MDD.
机译:由于长期暴露于负生命事件而导致的慢性胁迫会增加情绪和焦虑症的风险。虽然慢性应激可以改变对行为相关的基因表达,但这种变化的分子调节剂尚未完全确定。可以发挥作用的一个方法是DNA甲基化,将甲基加入核苷酸的表观遗传过程,主要是CPG上下文中的胞嘧啶,并且可以通过慢性胁迫诱导。尚不清楚慢性社会失败,人类社会压力模型,影响整个基因组的DNA甲基化模式。我们的研究通过使用称为甲基-SEQ的靶标捕获方法来解决诱导的捕获方法,以研究在暴露于14天的小鼠基因组的推定调节区域的DNA甲基化模式。通过双硫酸氢淀粉术在独立队列中复制了发现。鉴定了两个差异甲基化区域(DMRS)。一张DMR位于Drosha的Intron 9,并且它在应激小鼠中显示出降低的甲基化。此观察分为两个独立的队列中的一个。在染色体X的代际区域中鉴定了第二DMR,并且在胁迫小鼠中增加了该区域的甲基化。这种甲基化差异在两个独立的队列和主要抑郁症(MDD)后脑后死中复制。这些结果突出了以前未知的区域被慢性社会失败压力差异差异甲基化,并且可能参与MDD。

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