Enhancer RNAs: a missing regulatory layer in gene transcription

  • Renfang Mao
  • Yuanyuan Wu
  • Yue Ming
  • Yuanpei Xu
  • Shouyan Wang
  • Xia Chen
  • Xiaoying Wang
  • Yihui FanEmail author
Open Access


Enhancers and super-enhancers exert indispensable roles in maintaining cell identity through spatiotemporally regulating gene transcription. Meanwhile, active enhancers and super-enhancers also produce transcripts termed enhancer RNAs (eRNAs) from their DNA elements. Although enhancers have been identified for more than 30 years, widespread transcription from enhancers are just discovered by genome-wide sequencing and considered as the key to understand longstanding questions in gene transcription. RNA-transcribed enhancers are marked by histone modifications such as H3K4m1/2 and H3K27Ac, and enriched with transcription regulatory factors such as LDTFs, P300, CBP, BRD4 and MED1. Those regulatory factors might constitute a Mega-Trans-like complex to potently activate enhancers. Compared to mRNAs, eRNAs are quite unstable and play roles at local. Functionally, it has been shown that eRNAs promote formation of enhancer-promoter loops. Several studies also demonstrated that eRNAs help the binding of RNA polymerase II (RNAPII) or transition of paused RNAPII by de-association of the negative elongation factor (NELF) complex. Nevertheless, these proposed mechanisms are not universally accepted and still under controversy. Here, we comprehensively summarize the reported findings and make perspectives for future exploration. We also believe that super-enhancer derived RNAs (seRNAs) might be informative to understand the nature of super-enhancers.


enhancer RNAs (eRNAs) enhancers super-enhancers super-enhancer RNAs (seRNAs) gene transcription 



This work was supported by the Distinguished Professorship Program of Jiangsu Province to Y.F, the National Natural Science Foundation of China (31770935, 81641164, 81600386, 81471539, 30801350), the Natural Science Foundation of Nantong University (14Z022), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_1933), Undergraduate Training Program for Innovation (201710304030Z). We apologize to the many scientists who made contributions to the field, but were not cited due to space limitations.


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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Renfang Mao
    • 1
  • Yuanyuan Wu
    • 2
  • Yue Ming
    • 3
  • Yuanpei Xu
    • 3
  • Shouyan Wang
    • 2
  • Xia Chen
    • 2
  • Xiaoying Wang
    • 3
  • Yihui Fan
    • 2
    • 3
    Email author
  1. 1.Department of Pathophysiology, School of MedicineNantong UniversityNantongChina
  2. 2.Basic Medical Research Center, School of MedicineNantong UniversityNantongChina
  3. 3.Department of Immunology, School of MedicineNantong UniversityNantongChina

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