Environmentally sensitive hotspots in the methylome of the early human embryo.
Environmentally sensitive hotspots in the methylome of the early human embryo.
复制标题
早期人类胚胎甲基化组的环境敏感热点。
DOI：
10.7554/elife.72031
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发表时间：
2022-02-21
期刊：
影响因子：
7.7
通讯作者：
Prentice AM
中科院分区：
文献类型：
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作者：
Silver MJ;Saffari A;Kessler NJ;Chandak GR;Fall CHD;Issarapu P;Dedaniya A;Betts M;Moore SE;Routledge MN;Herceg Z;Cuenin C;Derakhshan M;James PT;Monk D;Prentice AM
在人类中，遗传自配子的DNA甲基化标记在胚胎甲基化构建之前，在受精后大部分被抹去。利用季节变化的自然实验，包括冈比亚农村饮食和营养状况的变化，我们分析了三个数据集，涵盖两个独立的儿童队列，并确定了259个CpGs，显示受孕季节（SoC）和DNA甲基化之间的一致关联。有机碳效应在婴儿期早期最为明显，在儿童中期有衰减的证据。soc相关的CpGs富集于亚稳态外显子、亲本起源特异性甲基化和种系差异甲基化区域，支持围孕期环境影响。在H1胚胎干细胞和胎儿组织中，许多soc相关的CpGs与活性转录增强子或位点重叠。一半的人受到独立于SoC的基因变异的影响，但不是由测量的遗传变异决定的。环境“热点”提供了孕周环境影响的记录，为研究将早期暴露与终身健康和疾病联系起来的表观遗传机制提供了宝贵资源。
In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed three datasets covering two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin-specific methylation and germline differentially methylated regions, supporting a periconceptional environmental influence. Many SoC-associated CpGs overlapped enhancers or sites of active transcription in H1 embryonic stem cells and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental ‘hotspots’ providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.