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

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@article{78a5ba8c493c4f5a9f28fcf0028c51ba,
title = "Identifiation of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development",
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 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. 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 = "Alternative splicing, development, embryonic brain, ionizing radiation, neuronal differentiation, p53 targets",
author = "Roel Quintens and Tine Verreet and Ann Janssen and Mieke Neefs and Liselotte Leysen and Arlette Michaux and Mieke Verslegers and Nada Samari and Giuseppe Pani and Joris Verheyde and Sarah Baatout and Rafi Benotmane",
note = "Score = 10",
year = "2015",
month = "2",
day = "13",
doi = "10.1242/bio.20149969",
language = "English",
volume = "4",
pages = "331--344",
journal = "Biology Open",
issn = "2046-6390",
publisher = "The Company of Biologists",

}

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TY - JOUR

T1 - Identifiation of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development

AU - Quintens, Roel

AU - Verreet, Tine

AU - Janssen, Ann

AU - Neefs, Mieke

AU - Leysen, Liselotte

AU - Michaux, Arlette

AU - Verslegers, Mieke

AU - Samari, Nada

AU - Pani, Giuseppe

AU - Verheyde, Joris

AU - Baatout, Sarah

AU - Benotmane, Rafi

N1 - Score = 10

PY - 2015/2/13

Y1 - 2015/2/13

N2 - 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 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. 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.

AB - 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 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. 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.

KW - Alternative splicing

KW - development

KW - embryonic brain

KW - ionizing radiation

KW - neuronal differentiation

KW - p53 targets

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_138827

UR - http://knowledgecentre.sckcen.be/so2/bibref/12393

U2 - 10.1242/bio.20149969

DO - 10.1242/bio.20149969

M3 - Article

VL - 4

SP - 331

EP - 344

JO - Biology Open

JF - Biology Open

SN - 2046-6390

ER -

ID: 200765