Project description:The polycomb group (PcG) protein, EZH2, possesses oncogenic properties for which the underlying mechanism is unclear. In this set of experiments, we sought to identify a robust set of Suz12-occupied gene promoters in prostate cancer cell lines. Genome-wide location analysis (ChIP-chip) of SUZ12 was performed in both the PC3 and LNCaP prostate cancer cell lines using an IgG ChIP-chip as a control. Keywords: ChIP-chip
Project description:The polycomb group (PcG) protein, EZH2, possesses oncogenic properties for which the underlying mechanism is unclear. In this set of experiments, we sought to identify a robust set of Suz12-occupied gene promoters in prostate cancer cell lines. Genome-wide location analysis (ChIP-chip) of SUZ12 was performed in both the PC3 and LNCaP prostate cancer cell lines using an IgG ChIP-chip as a control. There are total 3 hybridizations, including IgG ChIP-chip of PC3 cells, Suz12 ChIP-chip of PC3 and LNCaP cells.
Project description: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. Drug-seq assay followed by high-throughput sequencing (HT-seq).
Project description: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.