Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.
Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.
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DOI：
10.15252/msb.20156520
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发表时间：
2016-03-24
影响因子：
9.9
通讯作者：
Lehmann I
中科院分区：
文献类型：
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作者：
Bauer T;Trump S;Ishaque N;Thürmann L;Gu L;Bauer M;Bieg M;Gu Z;Weichenhan D;Mallm JP;Röder S;Herberth G;Takada E;Mücke O;Winter M;Junge KM;Grützmann K;Rolle-Kampczyk U;Wang Q;Lawerenz C;Borte M;Polte T;Schlesner M;Schanne M;Wiemann S;Geörg C;Stunnenberg HG;Plass C;Rippe K;Mizuguchi J;Herrmann C;Eils R;Lehmann I
表观遗传机制已成为产前环境暴露与晚年疾病风险之间的联系。在这里，我们通过绘制准妈妈及其新生儿的 DNA 甲基化、组蛋白修饰和转录图谱，以碱基对分辨率研究了与母亲吸烟相关的表观遗传变化。我们发现了广泛的全局差异甲基化，并仔细评估了这些变化，以将与基因型相关的 DNA 甲基化变化相关的环境分开。差异甲基化富含增强子元件和靶标，特别是与远端基因具有多种调节相互作用的“通勤”增强子。纵向全基因组亚硫酸氢盐测序表明，与母亲吸烟相关的 DNA 甲基化变化会持续数年。特别是在儿童中，产前环境暴露会导致染色质转变为过度活跃状态。综合 DNA 甲基化、组蛋白修饰和基因表达分析表明，增强子区域的差异甲基化比启动子或非调节元件的甲基化变化更常进行功能翻译。最后，我们发现针对 c-Jun N 末端激酶 2 (JNK2) 的通勤增强子的表观遗传失调与儿童早期肺功能受损有关。
Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype‐related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular “commuting” enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole‐genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non‐regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c‐Jun N‐terminal kinase 2 (JNK2) is linked to impaired lung function in early childhood.