Published Jan 06, 2020 on Dryad.
Cite this dataset
Kochmanski, Joseph; VanOeveren, Sarah E.; Patterson, Joseph R; Bernstein, Alison I. (2020). Developmental dieldrin exposure alters DNA methylation at genes related to dopaminergic neuron development and Parkinson’s disease in mouse midbrain [Dataset]. Dryad. https://doi.org/10.5061/dryad.s3n76mr
Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson’s disease (PD). Despite previous work showing a link between developmental dieldrin exposure and increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, the mechanism mediating this effect has not been identified. Here, we tested the hypothesis that developmental exposure to dieldrin increases neuronal susceptibility via genome-wide changes in DNA methylation. Starting at 8 weeks of age and prior to mating, female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin by feeding (every 3 days) throughout breeding, gestation, and lactation. At 12 weeks of age, pups were sacrificed and ventral mesencephalon, containing primarily substantia nigra, were microdissected. DNA was isolated and dieldrin-related changes in DNA methylation were assessed via reduced representation bisulfite sequencing (RRBS). We identified significant, sex-specific differentially methylated CpGs (DMCs) and regions (DMRs) by developmental dieldrin exposure (FDRNr4a2 and Lmx1b genes, which are involved in dopaminergic neuron development and maintenance. Developmental dieldrin exposure had distinct effects on the male and female epigenome. Together, our data suggest that developmental dieldrin exposure establishes sex-specific poised epigenetic states early in life. These poised epigenomes may mediate sensitivity to subsequent toxic stimuli and contribute to the development of late-life neurodegenerative disease, including PD.
This .zip file contains the supplementary tables and code used for the manuscript entitled "Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain" by Kochmanski et al. All supplementary tables are referenced in the text of the manuscript. Provided code is annotated, and is run in either R or on the linux command line.
National Institute of Environmental Health Sciences
National Institute of Environmental Health Sciences, Award: R00 ES024570
National Institute of Environmental Health Sciences, Award: R21 ES029205