The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis Academic Article uri icon

Overview

MeSH Major

  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Prostate
  • Prostatic Neoplasms
  • Receptors, Androgen

abstract

  • Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. 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 colocalized at the reprogrammed AR binding 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 cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.

publication date

  • November 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4707683

Digital Object Identifier (DOI)

  • 10.1038/ng.3419

PubMed ID

  • 26457646

Additional Document Info

start page

  • 1346

end page

  • 51

volume

  • 47

number

  • 11