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Series GSE94822 Query DataSets for GSE94822
Status Public on May 22, 2018
Title Super-enhancer Driven Core Regulatory Circuitry in MYCN-amplified Neuroblastoma [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Transcriptional dysregulation plays a major role in the development and progression of human tumors such as pediatric neuroblastoma. Therefore, we sought to elucidate the relationship between genes required for neuroblastoma cell growth and survival and the transcriptional core regulatory circuitry (CRC) that controls the gene expression program. A genome-scale CRISPR-Cas9 screen for oncogenic dependencies revealed that 143 genes are essential for cell survival and growth in neuroblastoma relative to other cancers, including many super-enhancer (SE) regulated transcription factors. Genome-wide occupancy analysis of transcription factor binding demonstrated that at least six of these transcription factors were both dependency genes and components of the CRC in MYCN-amplified neuroblastoma including: HAND2, ISL1, PHOX2B, GATA3, TBX2, and MEIS2. Binding sites for these transcription factors were clustered within a few hundred base pairs in their own enhancers and the enhancers of downstream target genes, which surprisingly included 40% of the independently determined neuroblastoma dependency genes. This profound level of transcriptional control of oncogenesis through self-reinforcing transcriptional circuits led us to test combinatorial pharmacological inhibition of transcriptional initiation and elongation, which synergistically induced tumor cell death, supporting Òdrugging transcriptionÓ as a means to advance the treatment of high risk neuroblastoma.
 
Overall design ChIP-Seq for transcription factors in neuroblastoma cell types
 
Contributor(s) Durbin AD, Zimmerman MW, Dharia NV, Abraham BJ, Balboni A, Weichert-Leahey N, He S, Krill-Burger JM, Vazquez F, Root DE, Tsherniak A, Hahn WC, Golub TR, Young RA, Stegmaier K, Look AT
Citation(s) 30127528
Submission date Feb 13, 2017
Last update date May 15, 2019
Contact name Richard A Young
E-mail(s) young_computation@wi.mit.edu
Phone 617-258-5219
Organization name Whitehead Institute for Biomedical Research
Lab Young Lab
Street address 9 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (16)
GSM2486153 BE2C PHOX2B [Lab: Look]
GSM2486155 BE2C HAND2_M19X [Lab: Look]
GSM2486156 BE2C Input [Lab: Look]
This SubSeries is part of SuperSeries:
GSE94824 Super-enhancer Driven Core Regulatory Circuitry in MYCN-amplified Neuroblastoma
Relations
BioProject PRJNA374532
SRA SRP099427

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE94822_RAW.tar 1.5 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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