Mapping the androgen receptor cistrome

Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in prostate cancer. Mapping the AR cistrome (cis-targets of a trans-acting factor across the genome) by ChIP-on-chip (chromatin immunoprecipitation on a microarray) discovers that the majority of AR-binding regions is far from the promoters of AR target genes and contains noncanonical AR responsive elements (ARE). Importantly, a noncanonical ARE is served as a cis-regulatory target of AR action in TMPRSS2, a gene fused to ETS transcription factors in the majority of prostate cancers. In addition other DNA sequence motifs are significantly enriched within the AR-binding regions and are bound by cooperating transcription factors FoxA1, GATA2, Oct1, and ETS1. These transcription factors cooperate in mediating the androgen response and offer potential new opportunities for therapeutic intervention.