Agonist and Antagonist Switch DNA Motifs Recognized by Human Androgen Receptor in Prostate Cancer

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Dec 24

PMID 25535248

Citations 54

Authors

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

Affiliations

Soon will be listed here.

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 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.

Citing Articles

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