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Series GSE84389 Query DataSets for GSE84389
Status Public on Nov 15, 2017
Title Network-based, cross-cohort discovery of transcriptional mechanisms presiding over maintenance of high-risk neuroblastoma subtype state
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Network-based analysis of neuroblastoma samples from two large cohorts identified master regulator proteins controlling the transcriptional state of three high-risk molecular subtypes. In particular, a TEAD4-MYCN positive feedback loop emerged as the core regulatory motif of a small protein module presiding over implementation and stability of the subtype associated with MYCN amplification. Specifically, MYCN transcriptionally activates TEAD4, which in turn activates MYCN both transcriptionally and post-translationally. The resulting MYCN-TEAD4 positive feedback loop plays a critical role in maintaining aberrant activity of a 10-protein regulatory module that causally regulates the transcriptional state of this subtype. Consistently, loss of TEAD4 activity induces core module activity collapse and abrogates neuroblastoma cell viability in vitro and in vivo, thus suggesting novel therapeutic strategies for this important childhood cancer.
Overall design Study of the transcriptional control by TEAD4 and MYCN positive feedback loop using RNA-seq profiles of TEAD4, WWTR1 and MYCN shRNA knockdowns in neuroblastoma BE2 cells. ChIP-Seq analysis using TEAD4 antibody in BE2 cells.
Contributor(s) Lopez G, Rajbhandari P
Citation(s) 29510988
Submission date Jul 14, 2016
Last update date Jul 25, 2021
Contact name Gonzalo Lopez
Organization name Mount Sinai School of Medicine
Department Genetics and Genomic Sciences
Street address 1399 Park avenue
City New York
State/province NY
ZIP/Postal code 10016
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (16)
GSM2232918 Control RNASeq 1
GSM2232919 Control RNASeq 2
GSM2232920 Control RNASeq 3
BioProject PRJNA329050
SRA SRP078495

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Supplementary file Size Download File type/resource
GSE84389_RAW.tar 2.6 Mb (http)(custom) TAR (of BED, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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