 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 17, 2018 |
| Title |
Direct interaction of MYCN and p53 regulate transcriptional responses in neuroblastoma [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The net transcriptome of a cancer cell is defined by relative levels of transcription factors, activators, suppressors and co-factors. These in turn are controlled by epigenetic, genetic and metabolic restraints. Here we used RNA-Seq, ChIP-qPCR, and ChIP-Seq to determine the impact of MYCN protein levels on p53 and MYCN mediated transcription in neuroblastoma, a p53 wild-type neural crest derived pediatric malignancy. Of note, about 25% of neuroblastoma is MYCN amplified and expresses 10-100 fold higher levels of MYCN protein than non-amplified tumors. We hypothesized that p53 functions would be globally altered by extreme MYCN levels and this could help to explain aggressive biology and poor long term survival which distinguishes MYCN-amplified neuroblastoma. In fact, we found that in the context of high MYCN levels, activation of p53 results in marked changes in transcription of specific p53 and MYCN target loci regulating apoptosis, DNA repair and cell cycle progression. Co-immunoprecipitation of endogenous and GST-fused proteins, as well as ChIP-qPCR confirms formation of p53/MYCN complexes and enrichment of both transcription factors at active loci. This p53/MYC interaction is independent of MYC/MAX complexes. Together, these data demonstrate MYCN to be a direct co-factor modulating p53 transcriptional output in MYCN amplified cancer.
|
| |
|
| Overall design |
To explore the MYCN binding at genomic locations under MYCN low and MYCN high conditions
|
| |
|
| Contributor(s) |
Agarwal S, Shohet J |
| Citation(s) |
29755654 |
| |
| Submission date |
Jun 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason Shohet |
| E-mail(s) |
jmshohet@txch.org
|
| Organization name |
Baylor College of Medicine
|
| Department |
Pediatrics
|
| Lab |
Hematology/Oncology
|
| Street address |
One Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (3) |
|
| This SubSeries is part of SuperSeries: |
| GSE83328 |
Direct interaction of MYCN and p53 regulate transcriptional responses in neuroblastoma |
|
| Relations |
| BioProject |
PRJNA325583 |
| SRA |
SRP076510 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE83317_RAW.tar |
67.9 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
