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

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          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.

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          Most cited references50

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          Non-coding RNA genes and the modern RNA world.

          S. Eddy (2001)
          Non-coding RNA (ncRNA) genes produce functional RNA molecules rather than encoding proteins. However, almost all means of gene identification assume that genes encode proteins, so even in the era of complete genome sequences, ncRNA genes have been effectively invisible. Recently, several different systematic screens have identified a surprisingly large number of new ncRNA genes. Non-coding RNAs seem to be particularly abundant in roles that require highly specific nucleic acid recognition without complex catalysis, such as in directing post-transcriptional regulation of gene expression or in guiding RNA modifications.
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            Polycomb silencers control cell fate, development and cancer.

            Polycomb group (PcG) proteins are epigenetic gene silencers that are implicated in neoplastic development. Their oncogenic function might be associated with their well-established role in the maintenance of embryonic and adult stem cells. In this review, we discuss new insights into the possible mechanisms by which PcGs regulate cellular identity, and speculate how these functions might be relevant during tumorigenesis.
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              ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs.

              Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 May 2020
                May 2020
                : 21
                : 10
                : 3711
                Affiliations
                [1 ]Center of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; melina.j.sedano@ 123456ttuhsc.edu (M.J.S.); Alana.L.Harrison@ 123456ttuhsc.edu (A.L.H.); ramesh.choudhari@ 123456ttuhsc.edu (R.C.); enrique.ramos@ 123456ttuhsc.edu (E.R.)
                [2 ]Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
                [3 ]Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; Mina.Zilaie@ 123456ttuhsc.edu
                [4 ]Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; chandrima.das@ 123456saha.ac.in
                [5 ]Homi Bhaba National Institute, Mumbai 400094, India
                Author notes
                [* ]Correspondence: shrikanth.gadad@ 123456ttuhsc.edu ; Tel.: +1-(915)-215-6431
                Author information
                https://orcid.org/0000-0001-7361-1652
                https://orcid.org/0000-0003-0030-5472
                Article
                ijms-21-03711
                10.3390/ijms21103711
                7279485
                32466143
                d1ee682e-14ac-49f8-b83c-ff5193873b09
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 May 2020
                : 24 May 2020
                Categories
                Review

                Molecular biology
                estrogen,erna,lncrna,breast cancer,transcription,gene-regulation,estrogen receptor
                Molecular biology
                estrogen, erna, lncrna, breast cancer, transcription, gene-regulation, estrogen receptor

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