Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer. EMBO J 2015 Feb 12;34(4):502-16
Date
12/24/2014Pubmed ID
25535248Pubmed Central ID
PMC4331004DOI
10.15252/embj.201490306Scopus ID
2-s2.0-84923062755 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
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.
Author List
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 KP, Huang TH, Lin S, Clinton SK, Li W, Jin VX, Wang QAuthor
Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Androgen Receptor AntagonistsAndrogens
Cell Proliferation
Chromatin Immunoprecipitation
DNA
Electrophoretic Mobility Shift Assay
Humans
Male
Prostatic Neoplasms
Receptors, Androgen
Reverse Transcriptase Polymerase Chain Reaction
