Journal
EPIGENETICS
Volume 9, Issue 7, Pages 934-941Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/epi.29024
Keywords
epigenetics; development; environment; DNA methylation; plasticity; environmental epigenomics; drift
Funding
- University of Michigan (UM) NIEHS/EPA Children's Environmental Health Center [P20 ES018171/RD834800, P01 ES022844/RD83543601]
- UM NIDDK Nutrition and Obesity Research Center [P30 DK089503]
- UM NIEHS Core Center [P30 ES017885]
- UM NIEHS Institutional Training Grant [T32 ES007062]
- NIH [K99 ES022221]
- National Center for Advancing Translational Sciences [2UL1TR000433]
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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.
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