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 (CabpIAP), 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 CabpIAP metastable epiallele. Pb exposure was associated with accelerated DNA hypermethylation in CabpIAP (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.
Bibliographical noteFunding Information:
This work was supported by the University of Michigan (UM) NIEHS/EPA Children’s Environmental Health Center P20 ES018171/RD834800 and P01 ES022844/RD83543601 as well as the UM NIDDK Nutrition and Obesity Research Center P30 DK089503, the UM NIEHS Core Center P30 ES017885, the UM NIEHS Institutional Training Grant T32 ES007062 (CF), NIH Grant K99 ES022221 (CF), and National Center for Advancing Translational Sciences Grant 2UL1TR000433 (JMG). The authors have no conflicts of interest and declare no competing financial interests.
- DNA methylation
- Environmental epigenomics