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Series GSE88746 Query DataSets for GSE88746
Status Public on Jul 13, 2017
Title Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies [ChIP-seq 1]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The success of targeted therapies hinges on our ability to understand the molecular and cellular mechanism of action of these agents. Here we modify various BET bromodomain inhibitors, an exemplar novel targeted therapy, to create functionally conserved compounds that are amenable to click-chemistry and can be used as molecular probes in vitro and in vivo. Using click-proteomics and click-sequencing we provide new mechanistic insights to explain the gene regulatory function of BRD4 and the transcriptional changes invoked by BET inhibitors. In mouse models of acute leukaemia, we use high resolution microscopy and flow cytometry to highlight the underappreciated heterogeneity of drug activity within tumour cells located in different tissue compartments. We also demonstrate the differential distribution and effects of the drug in normal and malignant cells in vivo. These data provide critical insights that reveal the cellular and molecular details for the efficacy and limitations of these agents. This study provides a framework for the pre-clinical assessment of other conventional and targeted therapies.
 
Overall design ChIPSeq for C/EBPα and β in MV4;11 cells
 
Contributor(s) Dawson MA, Grandi P, Tyler DS, Vappiani J, Lam EY
Citation(s) 28619718
Submission date Oct 14, 2016
Last update date May 15, 2019
Contact name Mark Dawson
E-mail(s) mark.dawson@petermac.org
Organization name Peter MacCallum Cancer Centre
Street address 305 Grattan Street
City Melbourne
State/province VIC
ZIP/Postal code 3000
Country Australia
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (3)
GSM2345026 MV4;11_C/EBPα_ChIP
GSM2345027 MV4;11_C/EBPβ_ChIP
GSM2345028 MV4;11_input DNA
This SubSeries is part of SuperSeries:
GSE88751 Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies
Relations
BioProject PRJNA348454
SRA SRP091550

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
GSE88746_RAW.tar 2.6 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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