|
| Status |
Public on Jul 01, 2014 |
| Title |
"Drug-seq": An Approach to Identify the Genomic Targets of Chemicals Identified by Functional Phenotypic Screens [GRO-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| 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 |
Global Run-On (GRO) assay followed by high-throughput sequencing (GRO-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
|
| Organization name |
HHMI/UCSD
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (4)
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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 |
|
| Relations |
| BioProject |
PRJNA241279 |
| SRA |
SRP040117 |
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