|
| Status |
Public on Jan 29, 2018 |
| Title |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
Other
Expression profiling by high throughput sequencing
|
| Summary |
Amplification of the locus encoding the oncogenic transcription factor MYCN is a defining feature of high-risk neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of MYCN perturbation in neuroblastoma. At oncogenic levels, MYCN associates with E-box binding motifs in an affinity-dependent manner, binding to strong canonical E-boxes at promoters and invading abundant weaker non-canonical E-boxes clustered at enhancers. Loss of MYCN leads to a global reduction in transcription, which is most pronounced at MYCN target genes with the greatest enhancer occupancy. These highly occupied MYCN target genes show tissue-specific expression and are linked to poor patient survival. The activity of genes with MYCN-occupied enhancers is dependent on the tissue-specific transcription factor TWIST1, which co-occupies enhancers with MYCN and is required for MYCN-dependent proliferation. These data implicate tissue-specific enhancers in defining often highly tumor-specific ‘MYC target gene signatures’ and identify disruption of the MYCN enhancer regulatory axis as a promising therapeutic strategy in neuroblastoma.
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| |
|
| Overall design |
Refer to individual Series
|
| Web link |
https://www.nature.com/articles/s41588-018-0044-9
|
| |
|
| Citation(s) |
29379199 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA215452 |
Identifying and targeting oncogenic Myc enhancer control in pediatric tumors |
BAYLOR COLLEGE OF MEDICINE |
Charles Yang Lin |
|
| Submission date |
Apr 11, 2016 |
| Last update date |
Jul 25, 2021 |
| Contact name |
James Bradner |
| E-mail(s) |
bradner_computation@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Bradner Lab
|
| Street address |
450 Brookline
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (4)
|
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16043 |
GeneChip® PrimeView™ Human Gene Expression Array (with External spike-in RNAs) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (144)
|
|
| This SuperSeries is composed of the following SubSeries:
|
| GSE80149 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [ARRAY] |
| GSE80150 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [ChIP_RX] |
| GSE80151 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [ChIP-seq] |
| GSE80152 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [ATAC-seq] |
| GSE80153 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [RNA-seq] |
| GSE100538 |
Enhancer invasion shapes MYCN dependent transcriptional amplification in neuroblastoma [ChIP-seq Th-MYCN] |
|
| Relations |
| BioProject |
PRJNA318035 |
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