1. Academic Validation
  2. Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor

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

  • Cell Rep. 2020 Jun 23;31(12):107803. doi: 10.1016/j.celrep.2020.107803.
Mei Yang 1 Ji Hoon Lee 1 Zhao Zhang 1 Richard De La Rosa 1 Mingjun Bi 1 Yuliang Tan 2 Yiji Liao 1 Juyeong Hong 1 Baowen Du 1 Yanming Wu 1 Jessica Scheirer 1 Tao Hong 3 Wei Li 4 Teng Fei 5 Chen-Lin Hsieh 6 Zhijie Liu 1 Wenbo Li 7 Michael G Rosenfeld 2 Kexin Xu 8
Affiliations

Affiliations

  • 1 Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • 2 Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, CA 92093, USA.
  • 3 Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Xiangya School of Medicine, Central South University, Changsha 410008, China.
  • 4 Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Division of Biostatistics, Dan L. Duncan Comprehensive Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • 5 College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
  • 6 Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • 7 Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA.
  • 8 Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: xuk3@uthscsa.edu.
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.

Keywords

ERα signaling; enhancer RNA; enhancer activity regulation; transcriptional repression.

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