Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells

被引:41
作者
Holmes, Kelly A. [1 ]
Hurtado, Antoni [1 ]
Brown, Gordon D. [1 ]
Launchbury, Rosalind [1 ]
Ross-Innes, Caryn S. [1 ]
Hadfield, James [1 ]
Odom, Duncan T. [1 ,2 ]
Carroll, Jason S. [1 ,2 ]
机构
[1] Li Ka Shing Ctr, Canc Res UK, Cambridge Res Inst, Cambridge CB2 0RE, England
[2] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England
基金
欧洲研究理事会;
关键词
COMPACTED CHROMATIN; C-MYC; FOXA1; IDENTIFICATION; ACTIVATION; REPRESSION; BEADARRAY; TAMOXIFEN; REVEALS; DOMAIN;
D O I
10.1073/pnas.1018863108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Estrogen receptor (ER) binds to distal enhancers within the genome and requires additional factors, such as the Forkhead protein FoxA1, for mediating chromatin interactions. We now show that the human Groucho protein, Transducin-like enhancer protein 1 (TLE1), positively assists some ER-chromatin interactions, a role that is distinct from its general role as a transcriptional repressor. We show that specific silencing of TLE1 inhibits the ability of ER to bind to a subset of ER binding sites within the genome, a phenomenon that results in perturbations in phospho-RNA Pol II recruitment. Furthermore, TLE1 is essential for effective ER-mediated cell division. We have discovered a distinct role for TLE1, as a necessary transcriptional component of the ER complex, where it facilitates ER-chromatin interactions.
引用
收藏
页码:2748 / 2753
页数:6
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