Functional Importance of eRNAs for Estrogen-dependent Transcriptional Activation Events

By Wenbo Li, D. Notani, Qi Ma, Bogdan Tanasa, Esperanza Núñez, A. Chen, Daria Merkurjev, Jie Zhang, K. Ohgi, Xiaoyuan Song and 4 more. Nature, 2013

950 citations recorded by the source corpus.

The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17β-oestradiol (E2)-bound oestrogen receptor α (ER-α) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer–promoter looping initiated by ER-α binding. Cohesin, present on many ER-α-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-α/eRNA-induced enhancer–promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/04e5acd0eda40a7747bd55ccddf43c4b9829af09

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Citations in the corpus

Super-enhancers in the control of cell identity and disease. (2013, positive): “Similarly, it would be useful to know if super-enhancers are transcribed, because enhancer RNAs (eRNAs) have been proposed to contribute to enhancer activity (Lai et al., 2013; Lam et al., 2013; Li et al., 2013; Ling et al., 2004; Mousavi et al., 2013; Orom et al., 2010).”
LncRNA-Dependent Mechanisms of Androgen Receptor-regulated Gene Activation Programs (2013, positive): “Considering the regulatory potential of enhancer RNAs (eRNAs) identified in recent studies 19,20 , lncRNAs may also be part of a broad transcription regulatory network.”
BRD4 and Cancer: going beyond transcriptional regulation (2018, background): “Many active ENHs have been shown to be site of active transcription for short (less than 200 nt) and bidirectional RNAs, which in turn assist ENHs in promoting target genes expression [40, 41].”
Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA (2017, background): “For instance, chromatin at the FOXC1 locus is stabilised by a complex including the oestrogen receptor alpha (ERa) and its ligand, as well as an eRNA transcribed from a FOXC1 enhancer [68].”
Linking Long Noncoding RNA Localization and Function. (2016, background): “Third, enhancer RNAs (eRNAs) are bidirectionally transcribed from enhancers by polymerase II (Pol II) and lack poly(A) tails (see Figure 1E in main text) [70,71] but have enhancer-like functions [72–74].”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, methodology): “Cross-linked chromatin complexes with RNA of interest are then isolated using streptavidin magnetic beads recognizing the biotin tag [46,102].”
Gene regulation by long non-coding RNAs and its biological functions (2020, positive): “…which recruits cohesin to form short-range (solid line) and long-range (dashed line) chromatin loops, thereby promoting contact between the NRIP1 enhancer and the promoters of NRIP1 and trefoil factor 1 ( TFF1 ), two of the several genes activated in response to ER activation 267 . d mechanisms.”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “Loss-of-function studies showed that degradation of eRNA is enough to reduce expression of neighboring genes (162, 211, 282).”