A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities

Long-range enhancers of transcription are a key component of the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these enhancers known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity....

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Autores principales: Banerjee, A. Raja, Kim, Yoon Jung, Kim, Tae Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227751/
https://www.ncbi.nlm.nih.gov/pubmed/25348400
http://dx.doi.org/10.1093/nar/gku1018
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author Banerjee, A. Raja
Kim, Yoon Jung
Kim, Tae Hoon
author_facet Banerjee, A. Raja
Kim, Yoon Jung
Kim, Tae Hoon
author_sort Banerjee, A. Raja
collection PubMed
description Long-range enhancers of transcription are a key component of the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these enhancers known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity. Through our systematic search for long-range elements that interact with the interferon-β gene, a model system for studying inducible transcription, we have identified a novel enhancer, which we have named L2 that regulates the expression of interferon-β. We have demonstrated its virus-inducible enhancer activity by analyzing epigenomic profiles, transcription factor association, nascent RNA production and activity in reporter assays. This enhancer exhibits intimately linked virus-inducible enhancer and bidirectional promoter activity that is largely dependent on a conserved Interferon Stimulated Response Element and robustly generates virus inducible eRNAs. Notably, its enhancer and promoter activities are fully retained in reporter assays even upon a complete elimination of its associated eRNA sequences. Finally, we show that L2 regulates IFNB1 expression by siRNA knockdown of eRNAs, and the deletion of L2 in a BAC transfection assay. Thus, L2 is a novel enhancer that regulates IFNB1 and whose eRNAs exert significant activity in vivo that is distinct from those activities recapitulated in the luciferase reporter assays.
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spelling pubmed-42277512014-11-21 A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities Banerjee, A. Raja Kim, Yoon Jung Kim, Tae Hoon Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Long-range enhancers of transcription are a key component of the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these enhancers known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity. Through our systematic search for long-range elements that interact with the interferon-β gene, a model system for studying inducible transcription, we have identified a novel enhancer, which we have named L2 that regulates the expression of interferon-β. We have demonstrated its virus-inducible enhancer activity by analyzing epigenomic profiles, transcription factor association, nascent RNA production and activity in reporter assays. This enhancer exhibits intimately linked virus-inducible enhancer and bidirectional promoter activity that is largely dependent on a conserved Interferon Stimulated Response Element and robustly generates virus inducible eRNAs. Notably, its enhancer and promoter activities are fully retained in reporter assays even upon a complete elimination of its associated eRNA sequences. Finally, we show that L2 regulates IFNB1 expression by siRNA knockdown of eRNAs, and the deletion of L2 in a BAC transfection assay. Thus, L2 is a novel enhancer that regulates IFNB1 and whose eRNAs exert significant activity in vivo that is distinct from those activities recapitulated in the luciferase reporter assays. Oxford University Press 2014-11-10 2014-10-27 /pmc/articles/PMC4227751/ /pubmed/25348400 http://dx.doi.org/10.1093/nar/gku1018 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Banerjee, A. Raja
Kim, Yoon Jung
Kim, Tae Hoon
A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title_full A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title_fullStr A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title_full_unstemmed A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title_short A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
title_sort novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227751/
https://www.ncbi.nlm.nih.gov/pubmed/25348400
http://dx.doi.org/10.1093/nar/gku1018
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