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Rapid and Efficient Spatiotemporal Monitoring of Normal and Aberrant Cytosine Methylation within Intact Zebrafish Embryos
Published on: August 18, 2022
Benzo[a]pyrene decreases global and gene specific DNA methylation during zebrafish development
Xiefan Fang1, Cammi Thornton, Brian E Scheffler
1Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, University, MS 38677, United States.
Environmental Toxicology and Pharmacology
|April 2, 2013
Summary
Benzo[a]pyrene (BaP) exposure in zebrafish embryos alters DNA methylation patterns, impacting gene regulation. This study reveals BaP as an epigenetic modifier affecting global and gene-specific DNA methylation in developing zebrafish.
Area of Science:
- Environmental epigenetics
- Developmental toxicology
- Molecular biology
Background:
- DNA methylation is crucial for gene regulation and is sensitive to environmental factors.
- Early-life exposure to contaminants like benzo[a]pyrene (BaP) can disrupt epigenetic processes.
- Zebrafish embryos are a valuable model for studying environmental impacts on development.
Purpose of the Study:
- To investigate the effects of benzo[a]pyrene (BaP) exposure on DNA methylation and gene expression in zebrafish embryos.
- To determine if BaP acts as an epigenetic modifier in a developing vertebrate model.
- To assess the impact of BaP on specific genes involved in cellular processes and cancer.
Main Methods:
- Zebrafish embryos were exposed to waterborne benzo[a]pyrene (BaP) at 24μg/L from 2.5 to 96 hours post-fertilization (hpf).
- Global and promoter-specific DNA methylation levels were quantified.
- Gene expression of vasa, cancer-related genes (rassf1, tert, c-jun, c-myca), and DNA methyltransferases (dnmt1, gnmt) was analyzed.
- DNA methyltransferase (DNMT) and glycine N-methyltransferase (GNMT) enzyme activities were measured.
Main Results:
- BaP exposure significantly decreased global cytosine methylation by 44.8% and vasa promoter methylation by 17%.
- Vasa gene expression increased by 33% following BaP exposure.
- Environmentally relevant BaP concentrations did not alter CpG island methylation or expression of tested cancer genes or DNA methyltransferases.
- Total DNMT activity remained unaffected, but GNMT enzyme activity moderately increased.
Conclusions:
- Benzo[a]pyrene (BaP) acts as an epigenetic modifier in zebrafish larvae, altering global and gene-specific DNA methylation.
- The study highlights the sensitivity of DNA methylation to environmental contaminants during early development.
- While high BaP concentrations impacted methylation, environmentally relevant levels did not affect tested cancer genes or core methylation machinery.
