The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis

Abstract

Master transcription factors interact with DNA to establish cell-type identity and to regulate gene expression in mammalian cells ^{1, 2} . The genome-wide map of these transcription factor binding sites has been termed the cistrome ³ . Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13, co-localized with the reprogrammed AR sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium towards transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.