PUBLICATION

Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

Authors
Aluru, N., Kuo, E., Helfrich, L.W., Karchner, S.I., Linney, E.A., Pais, J.E., Franks, D.G.
ID
ZDB-PUB-150304-6
Date
2015
Source
Toxicology and applied pharmacology   284(2): 142-51 (Journal)
Registered Authors
Linney, Elwood
Keywords
DNA methylation, TCDD, aryl hydrocarbon receptor, dioxin, dnmt, zebrafish development
MeSH Terms
  • Animals
  • DNA/genetics
  • DNA Methylation/drug effects*
  • Down-Regulation/drug effects
  • Embryo, Nonmammalian/drug effects
  • Gene Expression Regulation, Developmental/drug effects*
  • Methyltransferases/genetics
  • Promoter Regions, Genetic
  • Receptors, Aryl Hydrocarbon/genetics
  • Response Elements
  • Up-Regulation/drug effects
  • Zebrafish
  • Zebrafish Proteins/genetics
PubMed
25732252 Full text @ Tox. App. Pharmacol.
CTD
25732252
Abstract
DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for one hour from 4 to 5 hours post-fertilization (hpf) and sampled at 12, 24, 48, 72 and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2 and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping