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Series GSE164454 Query DataSets for GSE164454
Status Public on Mar 04, 2024
Title KDM4 inhibition disrupts the core regulatory transcriptional circuitry in MYCN-driven neuroblastoma [Cut&Tag]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary A small set of interconnected lineage-specific transcription factors (TFs) form a core regulatory circuitry (CRC) that establishes and maintains cell identity and grants selective dependencies of distinct cancer types. However, effective therapies to targeting CRC TFs remain lacking. Here, we show that the best-in-class KDM4 inhibitor QC6352 has a potent anticancer activity in MYCN-driven high-risk neuroblastoma and significantly represses the CRC TFs including MYCN, HAND2, ASCL1, PHOX2B by disrupting the super-enhancers that dominate the expression of CRC TFs. Furthermore, we have developed a combination therapy by integrating QC6352 into cytotoxic chemotherapy, which leads to a complete response of MYCN amplified tumors and a better animal survival. This study reveals that targeting histone lysine demethylase 4 family may transform into a therapeutic strategy in clinic for cancers driven by CRC TFs.
 
Overall design Examination of chromatin accessibility, histone modification post QC6352 treatment in BE2C.
 
Contributor(s) Jie F, Hongjian J, Jun Y
Citation(s) 38508144
Submission date Jan 08, 2021
Last update date Jun 03, 2024
Contact name Hongjian Jin
E-mail(s) hongjian.jin@STJUDE.ORG
Organization name St Jude Children's Research Hospital
Department Center for Applied Bioinformatics
Street address 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38015
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM5009775 CutTag_BE2C-DMSO-H3K27me3-001
GSM5009776 CutTag_BBE2C-DMSO-H3K27me3-002
GSM5009777 CutTag_BBE2C-QC-H3K27me3-001
This SubSeries is part of SuperSeries:
GSE164456 Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma
Relations
BioProject PRJNA690791
SRA SRP300908

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

Supplementary file Size Download File type/resource
GSE164454_RAW.tar 236.2 Mb (http)(custom) TAR (of BED, BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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