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

EMBO J. 2015 Feb 12;34(4):502-16. doi: 10.15252/embj.201490306. Epub 2014 Dec 22.


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 immunoprecipitation-exonuclease (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.

Keywords: ChIP‐exo; DNA motif switching; androgen receptor; prostate cancer; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgen Receptor Antagonists / chemistry*
  • Androgen Receptor Antagonists / metabolism
  • Androgens / chemistry*
  • Androgens / metabolism
  • Cell Proliferation / physiology
  • Chromatin Immunoprecipitation
  • DNA / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism*
  • Receptors, Androgen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • AR protein, human
  • Androgen Receptor Antagonists
  • Androgens
  • Receptors, Androgen
  • DNA