2. Academic Validation
  3. 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.
PMID: 32579929 DOI: 10.1016/j.celrep.2020.107803
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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