Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

Zhong Chen, Xun Lan, Jennifer M. Thomas-Ahner, Dayong Wu, Xiangtao Liu, Zhenqing Ye, Liguo Wang, Benjamin Sunkel, Cassandra Grenade, Junsheng Chen, Debra L. Zynger, Pearlly S. Yan, Jiaoti Huang, Kenneth P. Nephew, Tim H.M. Huang, Shili Lin, Steven K. Clinton, Wei Li, Victor X. Jin, Qianben Wang

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitationexonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles.

Original languageEnglish (US)
Pages (from-to)502-516
Number of pages15
JournalEMBO Journal
Issue number4
StatePublished - Feb 12 2015


  • Androgen receptor
  • ChIP-exo
  • DNA motif switching
  • Prostate cancer
  • Transcription factor

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • General Neuroscience


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