Androgen receptor genomic regulation

Abstract

The transcriptional activity of the androgen receptor (AR) is not only critical for the normal development and function of the prostate but also pivotal to the onset and progression of prostate cancer (PCa). The studies of AR transcriptional regulation were previously limited to a handful of AR-target genes. Owing to the development of various high-throughput genomic technologies, significant advances have been made in recent years. Here we discuss the discoveries of genome-wide androgen-regulated genes in PCa cell lines, animal models and tissues using expression microarray and sequencing, the mapping of genomic landscapes of AR using Combining Chromatin Immunoprecipitation (ChIP)-on-chip and ChIP-seq assays, the interplay of transcriptional cofactors in defining AR binding profiles, and the genomic regulation and AR reprogramming in advanced PCa.

Keywords: AR transcriptional regulation; AR-target genes; Androgen receptor (AR); ChIP-seq assays; Combining Chromatin Immunoprecipitation (ChIP)-on-chip; prostate cancer (PCa).

Figure 1

The cooperative regulatory network that controls AR chromatin binding and prostate gene expression. The genomic AR binding and expression of AR-responsive genes are tightly regulated by various mechanisms including histone modifications, pioneer factors, transcription factors, epigenetic modifiers and other AR coregulators, as well as long-range chromatin interactions and loopings.