1. Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish
- Author
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Kamstra, Jorke H., Hurem, Selma, Martin, Leonardo Martin, Lindeman, Leif C., Legler, Juliette, Oughton, Deborah, Salbu, Brit, Brede, Dag Anders, Lyche, Jan Ludvig, Aleström, Peter, One Health Toxicologie, dIRAS RA-1, One Health Toxicologie, and dIRAS RA-1
- Subjects
0301 basic medicine ,Genome instability ,Embryo, Nonmammalian ,Gametogenesis ,Epigenesis, Genetic ,0302 clinical medicine ,Transgenerational Effects ,Radiation, Ionizing ,zebra fish ,Zebrafish ,Regulation of gene expression ,DNA methylation ,Multidisciplinary ,biology ,Reproduction ,article ,apoptosis ,Gene Expression Regulation, Developmental ,biological marker ,Cell biology ,030220 oncology & carcinogenesis ,Medicine ,ionizing radiation ,enhancer region ,Differentially Expressed Genes (DEGs) ,DNA damage ,Offspring ,congenital malformation ,Science ,animal experiment ,embryo ,WGBS Data ,malignant neoplasm ,progeny ,Article ,Genomic Instability ,03 medical and health sciences ,promoter region ,follow up ,bisulfite ,Animals ,controlled study ,Differentially Methylated Regions (DMRs) ,Enhancer ,nonhuman ,DNA Methylation ,Zebrafish Proteins ,genomic instability ,biology.organism_classification ,Whole-genome Bisulfite Sequencing (WGBS) ,monitoring ,030104 developmental biology ,Differentially methylated regions ,fertilization ,gene expression ,DNA Damage - Abstract
Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.
- Published
- 2018