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The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pi...

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Autores principales: Battistelli, Cecilia, Sabarese, Giovanna, Santangelo, Laura, Montaldo, Claudia, Gonzalez, Frank J., Tripodi, Marco, Cicchini, Carla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461983/
https://www.ncbi.nlm.nih.gov/pubmed/30154449
http://dx.doi.org/10.1038/s41418-018-0170-z
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author Battistelli, Cecilia
Sabarese, Giovanna
Santangelo, Laura
Montaldo, Claudia
Gonzalez, Frank J.
Tripodi, Marco
Cicchini, Carla
author_facet Battistelli, Cecilia
Sabarese, Giovanna
Santangelo, Laura
Montaldo, Claudia
Gonzalez, Frank J.
Tripodi, Marco
Cicchini, Carla
author_sort Battistelli, Cecilia
collection PubMed
description The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity.
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spelling pubmed-64619832019-09-18 The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation Battistelli, Cecilia Sabarese, Giovanna Santangelo, Laura Montaldo, Claudia Gonzalez, Frank J. Tripodi, Marco Cicchini, Carla Cell Death Differ Article The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity. Nature Publishing Group UK 2018-08-28 2019-05 /pmc/articles/PMC6461983/ /pubmed/30154449 http://dx.doi.org/10.1038/s41418-018-0170-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Battistelli, Cecilia
Sabarese, Giovanna
Santangelo, Laura
Montaldo, Claudia
Gonzalez, Frank J.
Tripodi, Marco
Cicchini, Carla
The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title_full The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title_fullStr The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title_full_unstemmed The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title_short The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
title_sort lncrna hotair transcription is controlled by hnf4α-induced chromatin topology modulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461983/
https://www.ncbi.nlm.nih.gov/pubmed/30154449
http://dx.doi.org/10.1038/s41418-018-0170-z
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