Detection of differential DNA methylation in repetitive DNA of mice and humans perinatally exposed to bisphenol A.
Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next-generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples. Mice were treated during gestation and lactation to BPA in chow at 0, 50, or 50,000 ng/g levels and total BPA was measured in stratified human fetal liver tissue samples as low (non-detect to 0.83 ng/g), medium (3.5 to 5.79 ng/g), or high (35.44 to 96.76 ng/g). Transposon methylation changes were evident in human classes, families, and subfamilies, with the medium group exhibiting hypomethylation compared to both high and low BPA groups. Mouse repeat classes, families, and subfamilies did not respond to BPA with significantly detectable differential DNA methylation. In human samples, 1251 individual transposon loci were detected as differentially methylated by BPA exposure, but only 19 were detected in mice. Of note, this approach recapitulated the discovery of a previously known mouse environmentally labile metastable epiallele, Cabp(IAP). Thus, by querying repetitive DNA in both mouse and humans, we report the first known transposons in humans that respond to perinatal BPA exposure.
a Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.|b Department of Animal Science , College of Food, Agricultural, and Natural Resource Sciences, University of Minnesota , Minneapolis , MN , USA.
Christopher
C
Faulk
a Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.
Jung H
JH
Kim
c Department of Nutritional Sciences , University of Michigan , Ann Arbor , MI , USA.
Olivia S
OS
Anderson
a Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.
Muna S
MS
Nahar
a Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.
Tamara R
TR
Jones
d Department of Computational Medicine and Bioinformatics , Medical School, University of Michigan , Ann Arbor , MI , USA.
Maureen A
MA
Sartor
a Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.|c Department of Nutritional Sciences , University of Michigan , Ann Arbor , MI , USA.
Dana C
DC
Dolinoy
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D019175:DNA Methylation; D004251:DNA Transposable Elements; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D004251:DNA Transposable Elements; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Bisphenol A; DNA methylation; developmental origins of health and disease; environmental epigenomics; epigenetics; interindividual variation; next-generation sequencing; repetitive DNA; transposon