Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish
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...
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/4014 |
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| author | Sophia Murat El Houdigui Christelle Adam-Guillermin Olivier Armant |
| author_facet | Sophia Murat El Houdigui Christelle Adam-Guillermin Olivier Armant |
| author_sort | Sophia Murat El Houdigui |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:23:12Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:23:12Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cfcb7111481c4a38a0538890bd96977e2023-11-20T02:49:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012111401410.3390/ijms21114014Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in ZebrafishSophia Murat El Houdigui0Christelle Adam-Guillermin1Olivier Armant2PSE-ENV/SRTE/LECO, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Cadarache, 13115 Saint-Paul-Lez-Durance, FrancePSE-SANTE/SDOS/LMDN, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Cadarache, 13115 Saint-Paul-Lez-Durance, FrancePSE-ENV/SRTE/LECO, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Cadarache, 13115 Saint-Paul-Lez-Durance, FranceEmbryonic 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.https://www.mdpi.com/1422-0067/21/11/4014AOPdevelopmentionising radiationepigeneticDNA methylationtranscriptomics |
| spellingShingle | Sophia Murat El Houdigui Christelle Adam-Guillermin Olivier Armant Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish International Journal of Molecular Sciences AOP development ionising radiation epigenetic DNA methylation transcriptomics |
| title | Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish |
| title_full | Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish |
| title_fullStr | Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish |
| title_full_unstemmed | Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish |
| title_short | Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish |
| title_sort | ionising radiation induces promoter dna hypomethylation and perturbs transcriptional activity of genes involved in morphogenesis during gastrulation in zebrafish |
| topic | AOP development ionising radiation epigenetic DNA methylation transcriptomics |
| url | https://www.mdpi.com/1422-0067/21/11/4014 |
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