Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2020 Jun 25

PMID 32579929

Citations 17

Authors

Mei Yang

Ji Hoon Lee

Zhao Zhang

Richard de la Rosa

Mingjun Bi

Yuliang Tan

Yiji Liao

Juyeong Hong

Baowen Du

Yanming Wu

Jessica Scheirer

Tao Hong

Wei Li

Teng Fei

Chen-Lin Hsieh

Zhijie Liu

Wenbo Li

Michael G Rosenfeld

Kexin Xu

Affiliations

Soon will be listed here.

Abstract

The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure. By analyzing the genome-wide nascent transcript profiles in breast cancer cells, we identify a special group of eRNAs that are essential for estrogen-induced transcriptional repression. Using eRNAs of TM4SF1 and EFEMP1 as the paradigms, we find that these RNA molecules not only stabilize promoter-enhancer interactions but also recruit liganded estrogen receptor α (ERα) to particular enhancer regions, facilitate the formation of a functional transcriptional complex, and cause gene silencing. Interestingly, ERα is shown to directly bind with eRNAs by its DNA-binding domain. These eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Our work demonstrates a complete mechanism underlying the action of eRNAs in modulating and refining the locus-specific transcriptional program.

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