Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.

Abstract

The androgen receptor (AR) is a key transcription factor in prostate cancer (PCa), whose enhanced and altered functions are known drivers of cancer progression. A key aspect of this is reprogramming of the AR cistrome, which consists of genome-wide enhancer-binding sites through which AR regulates gene expression. The magnitude and biological impact of the AR cistrome are impacted by the AR itself, including the responses to ligand, as well as the organization of the associated DNA response elements, and availability of pioneer factors, cofactors, and noncoding RNAs, all of which contribute to a functional transcription complex. In this review, we will examine, in the context of PCa progression, the factors that affect the binding of AR and its interacting partners at enhancers, with a focus on AR cistrome reprogramming. We also discuss the clinical utility of targeting the AR-enhancer nucleoprotein complex and the potential of using the AR cistrome as a prognostic tool.