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Investigating the effects of DNA methylation on EE2 induction of estrogen receptor alpha gene expression in fathead minnows (Pimephales promelas)
Citation:
Fetke, J., R. Flick, J. Martinson, W. Huang, Mary Jean See, E. Pilgrim, AND A. Biales. Investigating the effects of DNA methylation on EE2 induction of estrogen receptor alpha gene expression in fathead minnows (Pimephales promelas). Society of Integrative and Comparative Biology, Austin, TX, January 03 - 07, 2020.
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:
Estrogens present in the environment 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. Despite this, little is known about epigenetic alterations, although these changes are believed to provide the critical linkage of gene expression with the development of adverse effects at higher biological levels. This study investigates alterations of DNA methylation of estrogen receptor á (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 exogenous estrogen, 17á-ethynylestradiol (EE2). Methylation differences were assessed across all CpG sites in a 2.5KB region encompassing exon 2 and 1.5KB upstream of the start site of the ERá gene by targeted deep sequencing of bisulfite treated DNA isolated from liver and brain tissue. Additionally, DNA methylation was assessed from fish depurated for 7 and 14 days to determine the kinetics of methylation. Finally, relationships between ERá methylation status and gene expression for individual fish were evaluated. Results from this work will provide information regarding the drivers of response to estrogens and the linkage between alterations in methylation status and gene expression.