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Status |
Public on Jul 01, 2014 |
Title |
"Drug-seq": An Approach to Identify the Genomic Targets of Chemicals Identified by Functional Phenotypic Screens [Drug-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Here we report an approach that has permitted us to uncover the sites and mechanisms of action of a drug, referred to as SD70, initially identified by phenotypic screening for inhibitors of ligand and genotoxic stress-induced translocations in prostate cancer cells. Based on synthesis of a derivatized form of SD70 that permits its application for a ChIP-seq-like approach, referred to as Drug-seq, we were next able to efficiently map the genome-wide binding locations of this small molecule, revealing that it largely co-localized with androgen receptor (AR) on regulatory enhancers. Based on these observations, we performed the appropriate global analyses to ascertain that SD70 inhibits the androgen-dependent AR program, and prostate cancer cell growth, acting, at least in part, by functionally inhibiting the jumonji (JMJ) domain-containing demethylase, KDM4C. Drug-seq represents a powerful strategy for new drug development by mapping genome-wide location of small molecules, a powerful adjunct to contemporary drug development strategies.
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Overall design |
Drug-seq assay followed by high-throughput sequencing (HT-seq).
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Contributor(s) |
Jin C, Yang L, Merkurjev D |
Citation(s) |
24928520 |
Submission date |
Mar 13, 2014 |
Last update date |
May 15, 2019 |
Contact name |
MICHAEL G ROSENFELD |
E-mail(s) |
mrosenfeld@ucsd.edu
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Organization name |
HHMI/UCSD
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Street address |
9500 Gilman Drive
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92093 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE55904 |
"Drug-seq": An Approach to Identify the Genomic Targets of Chemicals Identified by Functional Phenotypic Screens |
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Relations |
BioProject |
PRJNA241278 |
SRA |
SRP040116 |