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| Status |
Public on Apr 11, 2014 |
| Title |
Genome wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53 dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveals that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair
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| |
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| Overall design |
Examination of p63 and p53 binding sites in neonatal foreskin keratinocytes in response to adriamycin or cisplatin treatment
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| |
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| Contributor(s) |
McDade SS, McCancer DJ |
| Citation(s) |
24823795 |
| |
| Submission date |
Apr 10, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Simon S McDade |
| Organization name |
Queen's University Belfast
|
| Department |
CCRCB
|
| Street address |
97 Lisburn Road
|
| City |
Belfast |
| ZIP/Postal code |
BT9 7BL |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (13)
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| This SubSeries is part of SuperSeries: |
| GSE56640 |
Genome wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress |
|
| Relations |
| BioProject |
PRJNA244292 |
| SRA |
SRP041075 |
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