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. 2014 Jul;9(7):934-41.
doi: 10.4161/epi.29024. Epub 2014 May 1.

Longitudinal Epigenetic Drift in Mice Perinatally Exposed to Lead

Free PMC article

Longitudinal Epigenetic Drift in Mice Perinatally Exposed to Lead

Christopher Faulk et al. Epigenetics. .
Free PMC article


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.

Keywords: DNA methylation; development; drift; environment; environmental epigenomics; epigenetics; plasticity.


Figure 2. Absolute DNA methylation. DNA methylation percentage in four loci measured at two time points, day 22 (red) and 10 mo (green) in pairwise matched samples reveals epigenetic drift. Four lead exposure cohorts are indicated for each locus. Stars indicate significant changes in DNA methylation between time points.
Figure 3. Relative DNA methylation. Changes in DNA methylation in four loci indicate change in DNA methylation over time relative to day 22. Each exposure group is delineated and linear trend p-values are shown below. Stars indicate significant linear trends < 0.05 in DNA methylation.
Figure 1. Exposure paradigm. Dams were exposed 2 wk prior to mating to one of four levels of lead (Pb)-acetate in drinking water. Offspring exposure continued through gestation and lactation until postnatal day 22, upon which offspring were transferred and maintained in a Pb-free environment thereafter, until 10 mo of age.

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