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DNA Methylation Profile of Estrogen Receptor Alpha in Fish Exposed to EE2
Citation:
Fetke, J., R. Flick, J. Martinson, W. Huang, Mary Jean See, E. Pilgrim, AND A. Biales. DNA Methylation Profile of Estrogen Receptor Alpha in Fish Exposed to EE2. SETAC North America, Toronto, ON, CANADA, November 03 - 07, 2019.
Impact/Purpose:
This work will demonstrate the relationship between DNA methylation and gene expression in response to a known EDC. This has implications on susceptibility and interindividual extrapolation
Description:
Exogenous estrogens can interfere with endocrine function and cause decreased fecundity, fitness, and sperm production in fish, as well as feminization of male fish. Physiological effects and alterations of gene expression resulting from estrogen exposure have been thoroughly described in fish. However, little is known about epigenetic alterations, such as DNA methylation, although these changes are believed to be what links gene expression with the development of adverse effects at higher biological levels. This study investigates DNA methylation changes of a nuclear estrogen receptor (ERá) in brain and liver tissue in fathead minnows (Pimephales promelas) exposed to either 2.5 ng/L or 10 ng/L of the synthetic estrogen, 17á-ethynylestradiol (EE2). Methylation differences were assessed across all CpG sites in a 2.5KB region encompassing exon 1 and 1.5KB upstream of the start site of the ERá gene by targeted deep sequencing of bisulfite treated DNA isolated from treatment groups. Additionally, DNA methylation was assessed from fish depurated for 7 and 14 days to better understand the kinetics of methylation. Lastly, ERá methylation status and relationship to dose-dependent gene expression changes fish were evaluated. Results from this work will provide information about tissue-specific gene regulation in response to estrogens and how alterations in methylation status are associated with gene expression.