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 Nephew, Tim H M Huang, Shili Lin, Steven K. Clinton, Wei Li, Victor X. Jin, Qianben Wang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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
Pages (from-to)502-516
Number of pages15
JournalEMBO Journal
Volume34
Issue number4
DOIs
StatePublished - Feb 12 2015

Fingerprint

Nucleotide Motifs
Prostatic Neoplasms
Transcription Factors
Switches
Androgen Receptors
Ligands
Chromatin
Prostate
DNA
Androgen Receptor Antagonists
DNA sequences
Transcription
Transcriptome
Gene expression
Carcinogenesis
Cells
Tissue
human AR protein

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Chen, Z., Lan, X., Thomas-Ahner, J. M., Wu, D., Liu, X., Ye, Z., ... Wang, Q. (2015). Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer. EMBO Journal, 34(4), 502-516. https://doi.org/10.15252/embj.201490306

Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer. / Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M.; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L.; Yan, Pearlly S.; Huang, Jiaoti; Nephew, Kenneth; Huang, Tim H M; Lin, Shili; Clinton, Steven K.; Li, Wei; Jin, Victor X.; Wang, Qianben.

In: EMBO Journal, Vol. 34, No. 4, 12.02.2015, p. 502-516.

Research output: Contribution to journalArticle

Chen, Z, Lan, X, Thomas-Ahner, JM, Wu, D, Liu, X, Ye, Z, Wang, L, Sunkel, B, Grenade, C, Chen, J, Zynger, DL, Yan, PS, Huang, J, Nephew, K, Huang, THM, Lin, S, Clinton, SK, Li, W, Jin, VX & Wang, Q 2015, 'Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer', EMBO Journal, vol. 34, no. 4, pp. 502-516. https://doi.org/10.15252/embj.201490306
Chen, Zhong ; Lan, Xun ; Thomas-Ahner, Jennifer M. ; Wu, Dayong ; Liu, Xiangtao ; Ye, Zhenqing ; Wang, Liguo ; Sunkel, Benjamin ; Grenade, Cassandra ; Chen, Junsheng ; Zynger, Debra L. ; Yan, Pearlly S. ; Huang, Jiaoti ; Nephew, Kenneth ; Huang, Tim H M ; Lin, Shili ; Clinton, Steven K. ; Li, Wei ; Jin, Victor X. ; Wang, Qianben. / Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer. In: EMBO Journal. 2015 ; Vol. 34, No. 4. pp. 502-516.
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