Skip to main content
Journal cover image

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

Publication ,  Journal Article
Aluru, N; Kuo, E; Helfrich, LW; Karchner, SI; Linney, EA; Pais, JE; Franks, DG
Published in: Toxicol Appl Pharmacol
April 15, 2015

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 5nM TCDD for 1h from 4 to 5h 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 the 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Toxicol Appl Pharmacol

DOI

EISSN

1096-0333

Publication Date

April 15, 2015

Volume

284

Issue

2

Start / End Page

142 / 151

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Up-Regulation
  • Toxicology
  • Response Elements
  • Receptors, Aryl Hydrocarbon
  • Promoter Regions, Genetic
  • Polychlorinated Dibenzodioxins
  • Methyltransferases
  • Gene Expression Regulation, Developmental
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Aluru, N., Kuo, E., Helfrich, L. W., Karchner, S. I., Linney, E. A., Pais, J. E., & Franks, D. G. (2015). Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio). Toxicol Appl Pharmacol, 284(2), 142–151. https://doi.org/10.1016/j.taap.2015.02.016
Aluru, Neelakanteswar, Elaine Kuo, Lily W. Helfrich, Sibel I. Karchner, Elwood A. Linney, June E. Pais, and Diana G. Franks. “Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio).Toxicol Appl Pharmacol 284, no. 2 (April 15, 2015): 142–51. https://doi.org/10.1016/j.taap.2015.02.016.
Aluru N, Kuo E, Helfrich LW, Karchner SI, Linney EA, Pais JE, et al. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio). Toxicol Appl Pharmacol. 2015 Apr 15;284(2):142–51.
Aluru, Neelakanteswar, et al. “Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio).Toxicol Appl Pharmacol, vol. 284, no. 2, Apr. 2015, pp. 142–51. Pubmed, doi:10.1016/j.taap.2015.02.016.
Aluru N, Kuo E, Helfrich LW, Karchner SI, Linney EA, Pais JE, Franks DG. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio). Toxicol Appl Pharmacol. 2015 Apr 15;284(2):142–151.
Journal cover image

Published In

Toxicol Appl Pharmacol

DOI

EISSN

1096-0333

Publication Date

April 15, 2015

Volume

284

Issue

2

Start / End Page

142 / 151

Location

United States

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Up-Regulation
  • Toxicology
  • Response Elements
  • Receptors, Aryl Hydrocarbon
  • Promoter Regions, Genetic
  • Polychlorinated Dibenzodioxins
  • Methyltransferases
  • Gene Expression Regulation, Developmental