PUBLICATION

Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish

Authors
Kamstra, J.H., Sales, L.B., Aleström, P., Legler, J.
ID
ZDB-PUB-170418-7
Date
2017
Source
Epigenetics & chromatin   10: 20 (Journal)
Registered Authors
Aleström, Peter, Legler, Juliette, Sales, Liana Bastos
Keywords
5-Azacytidine, DNA methylation, Environmental stress, Epigenetics, Phthalate, Toxicology, Transgenerational, Zebrafish
Datasets
GEO:GSE84736
MeSH Terms
  • Animals
  • Azacitidine/toxicity*
  • Brain/drug effects
  • Brain/metabolism
  • DNA/chemistry
  • DNA/isolation & purification
  • DNA/metabolism*
  • DNA (Cytosine-5-)-Methyltransferase 1/genetics
  • DNA (Cytosine-5-)-Methyltransferase 1/metabolism
  • DNA Methylation/drug effects*
  • Diethylhexyl Phthalate/analogs & derivatives*
  • Diethylhexyl Phthalate/toxicity
  • Female
  • Gene Expression Regulation, Developmental/drug effects
  • Larva/drug effects
  • Larva/growth & development
  • Larva/metabolism
  • Liver/drug effects
  • Liver/metabolism
  • Male
  • Mutagenesis
  • Pregnancy
  • Sequence Analysis, DNA
  • Spermatozoa/drug effects
  • Spermatozoa/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/metabolism
PubMed
28413451 Full text @ Epigenetics Chromatin
Abstract
Exposure to environmental stressors during development may lead to latent and transgenerational adverse health effects. To understand the role of DNA methylation in these effects, we used zebrafish as a vertebrate model to investigate heritable changes in DNA methylation following chemical-induced stress during early development. We exposed zebrafish embryos to non-embryotoxic concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP, 30 µM) and the DNA methyltransferase 1 inhibitor 5-azacytidine (5AC, 10 µM). Direct, latent and transgenerational effects on DNA methylation were assessed using global, genome-wide and locus-specific DNA methylation analyses.
Following direct exposure in zebrafish embryos from 0 to 6 days post-fertilization, genome-wide analysis revealed a multitude of differentially methylated regions, strongly enriched at conserved non-genic elements for both compounds. Pathways involved in adipogenesis were enriched with the putative obesogenic compound MEHP. Exposure to 5AC resulted in enrichment of pathways involved in embryonic development and transgenerational effects on larval body length. Locus-specific methylation analysis of 10 differentially methylated sites revealed six of these loci differentially methylated in sperm sampled from adult zebrafish exposed during development to 5AC, and in first and second generation larvae. With MEHP, consistent changes were found at 2 specific loci in first and second generation larvae.
Our results suggest a functional role for DNA methylation on cis-regulatory conserved elements following developmental exposure to compounds. Effects on these regions are potentially transferred to subsequent generations.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping