期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 31, 期 23, 页码 4648-4662出版社
TAYLOR & FRANCIS INC
DOI: 10.1128/MCB.05934-11
关键词
-
资金
- USC Epigenome Center
- Norris Foundation
- Whittier Foundation
- NIH [R01 CA 109147, R01 CA 136924]
- U.S. National Institutes of Health [T32 CA009320, R37 CA082422]
- Concern Foundation
Nucleosome positioning at transcription start sites is known to regulate gene expression by altering DNA accessibility to transcription factors; however, its role at enhancers is poorly understood. We investigated nucleosome positioning at the androgen receptor (AR) enhancers of TMPRSS2, KLK2, and KLK3/PSA in prostate cancer cells. Surprisingly, a population of enhancer modules in androgen-deprived cultures showed nucleosome-depleted regions (NDRs) in all three loci. Under androgen-deprived conditions, NDRs at the TMPRSS2 enhancer were maintained by the pioneer AR transcriptional collaborator GATA-2. Androgen treatment resulted in AR occupancy, an increased number of enhancer modules with NDRs without changes in footprint width, increased levels of histone H3 acetylation (AcH3), and dimethylation (H3K4me2) at nucleosomes flanking the NDRs. Our data suggest that, in the absence of ligand, AR enhancers exist in an equilibrium in which a percentage of modules are occupied by nucleosomes while others display NDRs. We propose that androgen treatment leads to the disruption of the equilibrium toward a nucleosome-depleted state, rather than to enhancer de novo remodeling. This allows the recruitment of histone modifiers, chromatin remodelers, and ultimately gene activation. The receptive state described here could help explain AR signaling activation under very low ligand concentrations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据