Cell- and gene-specific regulation of primary target genes by the androgen receptor

Eric C. Bolton, Alex Y. So, Christina Chaivorapol, Christopher M. Haqq, Hao Li, Keith R. Yamamoto

Research output: Contribution to journalArticlepeer-review


The androgen receptor (AR) mediates the physiologic and pathophysiologic effects of androgens including sexual differentiation, prostate development, and cancer progression by binding to genomic androgen response elements (AREs), which influence transcription of AR target genes. The composition and context of AREs differ between genes, thus enabling AR to confer multiple regulatory functions within a single nucleus. We used expression profiling of an immortalized human prostate epithelial cell line to identify 205 androgen-responsive genes (ARGs), most of them novel. In addition, we performed chromatin immunoprecipitation to identify 524 AR binding regions and validated in reporter assays the ARE activities of several such regions. Interestingly, 67% of our AREs resided within ?50 kb of the transcription start sites of 84% of our ARGs. Indeed, most ARGs were associated with two or more AREs, and ARGs were sometimes themselves linked in gene clusters containing up to 13 AREs and 12 ARGs. AREs appeared typically to be composite elements, containing AR binding sequences adjacent to binding motifs for other transcriptional regulators. Functionally, ARGs were commonly involved in prostate cell proliferation, communication, differentiation, and possibly cancer progression. Our results provide new insights into cell- and gene-specific mechanisms of transcriptional regulation of androgen-responsive gene networks.

Original languageEnglish (US)
Pages (from-to)2005-2017
Number of pages13
JournalGenes and Development
Issue number16
StatePublished - Aug 15 2007
Externally publishedYes


  • Androgen receptor (AR)
  • Androgen response element (ARE)
  • Chromatin immunoprecipitation (ChiP)
  • Prostate cancer
  • Steroid receptor
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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