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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number107803
JournalCell Reports
Volume31
Issue number12
DOIs
StatePublished - Jun 23 2020

Keywords

  • ERα signaling
  • enhancer RNA
  • enhancer activity regulation
  • transcriptional repression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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