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Series GSE76147 Query DataSets for GSE76147
Status Public on Nov 15, 2016
Title A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm (ChIP-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary We combined loss-of-function RNA interference screening and a high-throughput drug toxicity screening to define novel therapeutic targets in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy for which no curative therapy exists. The E-box transcription factor TCF4 emerged as the master transcriptional regulator of the BPDCN oncogenic program, a finding that can be exploited for the accurate molecular diagnosis of BPDCN. Genetic interference with the TCF4-dependent network induced a rewiring of BPDCN gene expression, resulting in apoptosis. Treatment of BPDCN lines with bromodomain and extra-terminal domain inhibitors (BETi's) down regulated TCF4 and its target gene network, inducing apoptosis both in vitro and retarding growth of BPDCN xenografts in vivo, supporting the clinical evaluation of BETi's in this lethal cancer.
Overall design We performed chromatin immunoprecipitation coupled to NGS (ChIP-Seq) to identify genomic binding sites for TCF4 in both cell lines, using an anti- TCF4 rabbit monoclonal antibody that we developed for this purpose. We performed BRD4 and RNA Pol2 ChIP-Seq before and after JQ1 treatment, in both the Cal-1 and Gen2.2 BPDCN lines.
Citation(s) 27846392
Submission date Dec 18, 2015
Last update date May 15, 2019
Contact name Louis M. Staudt
Phone 301-402-1892
Organization name National Cancer Institute
Department Lymphoid Malignancies Branch
Lab Louis M Staudt
Street address 9000 Rockville Pike, Bldg 10, Rm 4N114
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (16)
GSM1975017 Cal-1 IgG Control
GSM1975018 Cal-1 TCF4 mAb
GSM1975019 Gen2.2 IgG Control
BioProject PRJNA306431
SRA SRP067566

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Supplementary file Size Download File type/resource
GSE76147_RAW.tar 63.4 Mb (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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