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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Longitudinal epigenetic drift in mice perinatally exposed to lead
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Longitudinal epigenetic drift in mice perinatally exposed to lead

机译：围生期暴露于铅的小鼠的纵向表观遗传漂移

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摘要

An understanding of the natural change in DNA methylation over time, defined as "epigenetic drift," will inform the study of environmental effects on the epigenome. This study investigates epigenetic drift in isogenic mice exposed perinatally to lead (Pb) acetate at four concentrations, 0 ppm (control), 2.1 ppm (low), 16 ppm (medium), and 32 ppm (high) prior to conception through weaning, then followed until 10 months of age. Absolute values of DNA methylation in a transposon-associated metastable locus, Cdk5-activator binding protein (Cabp(IAP)), and three imprinted loci (Igf2, Igf2r, and H19) were obtained from tail tissue in paired samples. DNA methylation levels in the controls increased over time at the imprinted Igf2 and Igf2r loci (both P = 0.0001), but not at the imprinted H19 locus or the Cabp(IAP) metastable epiallele. Pb exposure was associated with accelerated DNA hypermethylation in Cabp(IAP) (P = 0.0209) and moderated hypermethylation in Igf2r (P = 0.0447), and with marginally accelerated hypermethylation at H19 (P = 0.0847). In summary, the presence and magnitude of epigenetic drift was locus-dependent, and enhancement of drift was mediated by perinatal Pb exposure, in some, but not all, loci.
机译：对DNA甲基化随时间的自然变化的理解（定义为“表观遗传漂移”）将有助于研究环境对表观基因组的影响。这项研究调查了在通过断奶受孕之前，围产期暴露于四种浓度，0 ppm（对照），2.1 ppm（低），16 ppm（中）和32 ppm（高）的乙酸铅（Pb）的同基因小鼠的表观遗传漂移，然后跟进直到10个月大。从配对样品的尾部组织中获得与转座子相关的亚稳态基因座，Cdk5激活物结合蛋白（Cabp（IAP））和三个印迹基因座（Igf2，Igf2r和H19）的DNA甲基化的绝对值。印迹中的Igf2和Igf2r基因座上的DNA甲基化水平随时间增加（均为P = 0.0001），但印迹H19位点或Cabp（IAP）亚稳态的等位基因则没有。铅暴露与Cabp（IAP）中的DNA过度甲基化加速（P = 0.0209）和Igf2r中的中度过度甲基化（P = 0.0447）有关，并且与H19的边缘甲基化略有加速（P = 0.0847）。总之，表观遗传漂移的存在和程度取决于基因座，并且漂移的增强是由围产期Pb暴露（在一些但不是全部基因座中）介导的。

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