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Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development

Roel Quintens, Tine Verreet, Ann Janssen, Mieke Neefs, Liselotte Leysen, Arlette Michaux, Mieke Verslegers, Nada Samari, Giuseppe Pani (UGent) , Joris Verheyde, et al.
(2015) BIOLOGY OPEN. 4(3). p.331-344
Author
Organization
Abstract
Ionizing radiation is a potent activator of the tumor suppressor gene p53, which itself regulates the transcription of genes involved in canonical pathways such as the cell cycle, DNA repair and apoptosis as well as other biological processes like metabolism, autophagy, differentiation and development. In this study, we performed a meta-analysis on gene expression data from different in vivo and in vitro experiments to identify a signature of early radiation-responsive genes which were predicted to be predominantly regulated by p53. Moreover, we found that several genes expressed different transcript isoforms after irradiation in a p53-dependent manner. Among this gene signature, we identified novel p53 targets, some of which have not yet been functionally characterized. Surprisingly, in contrast to genes from the canonical p53-regulated pathways, our gene signature was found to be highly enriched during embryonic and post-natal brain development and during in vitro neuronal differentiation. Furthermore, we could show that for a number of genes, radiation-responsive transcript variants were upregulated during development and differentiation, while radiation non-responsive variants were not. This suggests that radiation exposure of the developing brain and immature cortical neurons results in the p53-mediated activation of a neuronal differentiation program. Overall, our results further increase the knowledge of the radiation-induced p53 network of the embryonic brain and provide more evidence concerning the importance of p53 and its transcriptional targets during mouse brain development.
Keywords
DNA-DAMAGE RESPONSE, EMBRYONIC STEM-CELLS, TUMOR SUPPRESSION, CEREBRAL-CORTEX, IONIZING-RADIATION, PROFILING REVEALS, BOMB SURVIVORS, P53, EXPRESSION, DIFFERENTIATION, Development, Alternative splicing, Embryonic brain, Ionizing radiation, p53 targets, Neuronal differentiation

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MLA
Quintens, Roel, et al. “Identification of Novel Radiation-Induced P53-Dependent Transcripts Extensively Regulated during Mouse Brain Development.” BIOLOGY OPEN, vol. 4, no. 3, 2015, pp. 331–44, doi:10.1242/bio.20149969.
APA
Quintens, R., Verreet, T., Janssen, A., Neefs, M., Leysen, L., Michaux, A., … Benotmane, M. A. (2015). Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development. BIOLOGY OPEN, 4(3), 331–344. https://doi.org/10.1242/bio.20149969
Chicago author-date
Quintens, Roel, Tine Verreet, Ann Janssen, Mieke Neefs, Liselotte Leysen, Arlette Michaux, Mieke Verslegers, et al. 2015. “Identification of Novel Radiation-Induced P53-Dependent Transcripts Extensively Regulated during Mouse Brain Development.” BIOLOGY OPEN 4 (3): 331–44. https://doi.org/10.1242/bio.20149969.
Chicago author-date (all authors)
Quintens, Roel, Tine Verreet, Ann Janssen, Mieke Neefs, Liselotte Leysen, Arlette Michaux, Mieke Verslegers, Nada Samari, Giuseppe Pani, Joris Verheyde, Sarah Baatout, and Mohammed Abderrafi Benotmane. 2015. “Identification of Novel Radiation-Induced P53-Dependent Transcripts Extensively Regulated during Mouse Brain Development.” BIOLOGY OPEN 4 (3): 331–344. doi:10.1242/bio.20149969.
Vancouver
1.
Quintens R, Verreet T, Janssen A, Neefs M, Leysen L, Michaux A, et al. Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development. BIOLOGY OPEN. 2015;4(3):331–44.
IEEE
[1]
R. Quintens et al., “Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development,” BIOLOGY OPEN, vol. 4, no. 3, pp. 331–344, 2015.
@article{6855109,
  abstract     = {{Ionizing radiation is a potent activator of the tumor suppressor gene p53, which itself regulates the transcription of genes involved in canonical pathways such as the cell cycle, DNA repair and apoptosis as well as other biological processes like metabolism, autophagy, differentiation and development. In this study, we performed a meta-analysis on gene expression data from different in vivo and in vitro experiments to identify a signature of early radiation-responsive genes which were predicted to be predominantly regulated by p53. Moreover, we found that several genes expressed different transcript isoforms after irradiation in a p53-dependent manner. Among this gene signature, we identified novel p53 targets, some of which have not yet been functionally characterized. Surprisingly, in contrast to genes from the canonical p53-regulated pathways, our gene signature was found to be highly enriched during embryonic and post-natal brain development and during in vitro neuronal differentiation. Furthermore, we could show that for a number of genes, radiation-responsive transcript variants were upregulated during development and differentiation, while radiation non-responsive variants were not. This suggests that radiation exposure of the developing brain and immature cortical neurons results in the p53-mediated activation of a neuronal differentiation program. Overall, our results further increase the knowledge of the radiation-induced p53 network of the embryonic brain and provide more evidence concerning the importance of p53 and its transcriptional targets during mouse brain development.}},
  author       = {{Quintens, Roel and Verreet, Tine and Janssen, Ann and Neefs, Mieke and Leysen, Liselotte and Michaux, Arlette and Verslegers, Mieke and Samari, Nada and Pani, Giuseppe and Verheyde, Joris and Baatout, Sarah and Benotmane, Mohammed Abderrafi}},
  issn         = {{2046-6390}},
  journal      = {{BIOLOGY OPEN}},
  keywords     = {{DNA-DAMAGE RESPONSE,EMBRYONIC STEM-CELLS,TUMOR SUPPRESSION,CEREBRAL-CORTEX,IONIZING-RADIATION,PROFILING REVEALS,BOMB SURVIVORS,P53,EXPRESSION,DIFFERENTIATION,Development,Alternative splicing,Embryonic brain,Ionizing radiation,p53 targets,Neuronal differentiation}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{331--344}},
  title        = {{Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development}},
  url          = {{http://doi.org/10.1242/bio.20149969}},
  volume       = {{4}},
  year         = {{2015}},
}
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