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Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 11, International Journal of Molecular Sciences, Vol 21, Iss 4014, p 4014 (2020), International Journal of Molecular Sciences, MDPI, 2020, 21 (11), pp.4014. ⟨10.3390/ijms21114014⟩
- Publication Year :
- 2020
-
Abstract
- Embryonic development is particularly vulnerable to stress and DNA damage, as mutations can accumulate through cell proliferation in a wide number of cells and organs. However, the biological effects of chronic exposure to ionising radiation (IR) at low and moderate dose rates (&lt<br />6 mGy/h) remain largely controversial, raising concerns for environmental protection. The present study focuses on the molecular effects of IR (0.005 to 50 mGy/h) on zebrafish embryos at the gastrula stage (6 hpf), at both the transcriptomics and epigenetics levels. Our results show that exposure to IR modifies the expression of genes involved in mitochondrial activity from 0.5 to 50 mGy/h. In addition, important developmental pathways, namely, the Notch, retinoic acid, BMP and Wnt signalling pathways, were altered at 5 and 50 mGy/h. Transcriptional changes of genes involved in the morphogenesis of the ectoderm and mesoderm were detected at all dose rates, but were prominent from 0.5 to 50 mGy/h. At the epigenetic level, exposure to IR induced a hypomethylation of DNA in the promoter of genes that colocalised with both H3K27me3 and H3Kme4 histone marks and correlated with changes in transcriptional activity. Finally, pathway enrichment analysis demonstrated that the DNA methylation changes occurred in the promoter of important developmental genes, including morphogenesis of the ectoderm and mesoderm. Together, these results show that the transcriptional program regulating morphogenesis in gastrulating embryos was modified at dose rates greater than or equal to 0.5 mGy/h, which might predict potential neurogenesis and somitogenesis defects observed at similar dose rates later in development.
- Subjects :
- Transcriptional Activation
animal structures
[SDV]Life Sciences [q-bio]
Organogenesis
Article
lcsh:Chemistry
Mesoderm
transcriptomics
Radiation, Ionizing
Ectoderm
Morphogenesis
Animals
gastrulation
Promoter Regions, Genetic
germ layer
lcsh:QH301-705.5
AOP
development
DNA methylation
ionising radiation
Gene Expression Profiling
Computational Biology
Gene Expression Regulation, Developmental
zebrafish
lcsh:Biology (General)
lcsh:QD1-999
embryonic structures
Transcriptome
epigenetic
Subjects
Details
- ISSN :
- 14220067 and 16616596
- Volume :
- 21
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.pmid.dedup....5aa30152da13e44d956cf6b786b2e72f