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Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer
Author(s) -
Chen Zhong,
Lan Xun,
ThomasAhner 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 P,
Huang Tim HM,
Lin Shili,
Clinton Steven K,
Li Wei,
Jin Victor X,
Wang Qianben
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490306
Subject(s) - biology , prostate cancer , agonist , androgen receptor , receptor , antagonist , androgen , dna , cancer , cancer research , microbiology and biotechnology , computational biology , genetics , bioinformatics , endocrinology , hormone
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 (Ch IP ‐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.