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
SN - 2046-6390
VL - 4
SP - 331
EP - 344
JO - Biology Open
JF - Biology Open
ER -