Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

Abstract

Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a , gmnn and vegfab . A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.

Current evidence for a role of epigenetic mechanisms in response to ionizing radiation in an ecotoxicological context

“…offspring, but interestingly these effects were diminished in F2 offspring (Lindeman et al 2019, submitted). Although only exposed embryo's were analysed similar changes in histone markes were found for Atlantic salmon (Salmo salar) at higher dose rates (Lindeman et al 2019).…”

“…These methylation changes could be linked to changes in gene pathways and adverse effects found in progeny (Hurem et al 2017;Hurem et al 2018b). In the same exposure study, miRNA expression was measured in first filial offspring and histone marks H3K4me3, H3K9me4 and H3K27me3 at 3 specific loci (Lindeman et al 2019). There were 23 differentially expressed miRNAs indicating a multifaceted response to ionising radiation exposure (Martin et al 2019, in preparation).…”

Stage-Specific Effects of Ionizing Radiation during Early Development

“…These observations suggest that cell cycle checkpoints are a key factor for preserving genome integrity. Lindelman et al [11] reported that exposing zebrafish embryos to radiation for 3 h beginning at 2.5 hpf (256-cell stage) induced locus-specific changes in the enrichment of histone modifications. Similar results were observed when Atlantic salmon embryos were exposed to radiation from the 1-cell stage to the early gastrula stage [11].…”

“…Lindelman et al [11] reported that exposing zebrafish embryos to radiation for 3 h beginning at 2.5 hpf (256-cell stage) induced locus-specific changes in the enrichment of histone modifications. Similar results were observed when Atlantic salmon embryos were exposed to radiation from the 1-cell stage to the early gastrula stage [11]. To assess whether this change affects chromatin structure or organization, additional experiments must be carried out.…”

“…Recently, the specific cellular and molecular mechanisms underlying the response to ionizing radiation during the preimplantation period have been analyzed [8][9][10][11] and may explain the differences in sensitivity and response to ionizing radiation between each developmental period. Given that there are detailed reviews about the mechanisms of the response to ionizing radiation during the organogenesis and fetus periods [12][13][14], we will focus on the variation in sensitivity and response to radiation during the preimplantation (before gastrulation) period and discuss the underlying cellular and molecular mechanisms in this review.…”