Profiling DNA methylation patterns of zebrafish liver associated with parental high dietary arachidonic acid

PLoS One. 2019 Aug 9;14(8):e0220934. doi: 10.1371/journal.pone.0220934. eCollection 2019.


Diet has been shown to influence epigenetic key players, such as DNA methylation, which can regulate the gene expression potential in both parents and offspring. Diets enriched in omega-6 and deficient in omega-3 PUFAs (low dietary omega-3/omega-6 PUFA ratio), have been associated with the promotion of pathogenesis of diseases in humans and other mammals. In this study, we investigated the impact of increased dietary intake of arachidonic acid (ARA), a physiologically important omega-6 PUFA, on 2 generations of zebrafish. Parental fish were fed either a low or a high ARA diet, while the progeny of both groups were fed the low ARA diet. We screened for DNA methylation on single base-pair resolution using reduced representation bisulfite sequencing (RRBS). The DNA methylation profiling revealed significant differences between the dietary groups in both parents and offspring. The majority of differentially methylated loci associated with high dietary ARA were found in introns and intergenic regions for both generations. Common loci between the identified differentially methylated loci in F0 and F1 livers were reported. We described overlapping gene annotations of identified methylation changes with differential expression, but based on a small number of overlaps. The present study describes the diet-associated methylation profiles across genomic regions, and it demonstrates that parental high dietary ARA modulates DNA methylation patterns in zebrafish liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology*
  • Body Weight / drug effects
  • Cluster Analysis
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Diet*
  • Feeding Behavior / drug effects
  • Gene Expression Regulation / drug effects
  • Genetic Loci
  • Genome
  • Liver / drug effects
  • Liver / metabolism*
  • Molecular Sequence Annotation
  • Zebrafish / genetics*


  • Arachidonic Acid

Grant support

This research was financed through The Research Council of Norway ( EpiSip 228877 (KHS) and EpiFeedFish 225250/E40 (KHS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.