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Review
. 2020 May 25;21(10):3711.
doi: 10.3390/ijms21103711.

Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

Melina J Sedano  1   2 , Alana L Harrison  1   2 , Mina Zilaie  3 , Chandrima Das  4   5 , Ramesh Choudhari  1 , Enrique Ramos  1 , Shrikanth S Gadad  1   2   3
Affiliations
Review

Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

Melina J Sedano et al. Int J Mol Sci. .

Abstract

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be "junk" DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

Keywords: breast cancer; eRNA; estrogen; estrogen receptor; gene-regulation; lncRNA; transcription.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simplistic representation of estrogen receptor (ER) signaling (genomic activity). Estrogen (E2)-bound ERα, is recruited to target promoters at estrogen response elements (EREs). E2 binds ERα and recruits coactivator complexes (CoA) to modulate gene transcription. Tamoxifen (TAM) and fulvestrant (Ful) are E2 antagonists. UPS: ubiquitin–proteasome system; CoR: Coregulator.
Figure 2
Figure 2
eRNA transcription at enhancers. Pol II transcribes eRNAs from active enhancers marked with H3K4me1 and H3K27ac.
Figure 3
Figure 3
A plausible mechanism of estrogen-induced enhancer RNA (eRNA) function in chromatin looping.
Figure 4
Figure 4
Known long non-coding RNA (lncRNA) mechanisms of action in regulating estrogen-dependent transcription. (TF: transcription factor; ERα estrogen receptor alpha; ERE: estrogen response element).
See this image and copyright information in PMC

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