GSE28950
TMPRSS2-ERG, HDACs and EZH2 are involved in an AR-centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (ChIP-Seq data)
Deregulation of the Androgen Receptor (AR) transcriptional network is a common hallmark in prostate cancers. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of cofactors. In prostate cancers, AR transcription collaborators are frequently aberrantly over-expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, the prostate cancer recurrent fusion gene, ERG, was shown to promote tumor progression by acting as a repressor of AR signaling. However, the exact mechanics and the functional consequences associated with this crosstalk between ERG and AR still remains relatively unknown. Interestingly, through chromatin immunoprecipitation coupled with massively parallel sequencing, we discover that ERG and other commonly over-expressed transcriptional co-repressors (HDAC1, HDAC2, HDAC3 and EZH2) are wired into an AR-centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. We show that ERG represses several AR target genes involved in epithelial differentiation. Furthermore, we demonstrated that suppression of the androgen-induced gene, Vinculin, by ERG and histone deacetylases increases cancer cell invasiveness. From our results, we propose that ERG, histone deactelyases and the histone methyltransferase, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, in part through modulating the transcriptional output of AR. Overall design: Genome-wide binding analysis of AR, ERG, HDAC1, HDAC2, HDAC3 and EZH2 in VCaP with and without DHT (dihydrotestosterone) stimulation using ChIP-Seq. 15 samples including 1 control (input).