PUBLICATION

Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish

Authors
Murat El Houdigui, S., Adam-Guillermin, C., Armant, O.
ID
ZDB-PUB-200610-1
Date
2020
Source
International Journal of Molecular Sciences   21(11): (Journal)
Registered Authors
Armant, Olivier
Keywords
AOP, DNA methylation, development, epigenetic, gastrulation, germ layer, ionising radiation, transcriptomics, zebrafish
Datasets
GEO:GSE146198
MeSH Terms
  • Animals
  • Computational Biology/methods
  • DNA Methylation/radiation effects*
  • Ectoderm/embryology
  • Ectoderm/metabolism
  • Ectoderm/radiation effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/radiation effects*
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Mesoderm/radiation effects
  • Morphogenesis/genetics*
  • Organogenesis/genetics*
  • Promoter Regions, Genetic*
  • Radiation, Ionizing*
  • Transcriptional Activation/radiation effects*
  • Transcriptome
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed
32512748 Full text @ Int. J. Mol. Sci.
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 (< 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes