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....
Autores principales: | , , |
---|---|
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 |
_version_ | 1782343866475610112 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4227751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT banerjeearaja anovelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities AT kimyoonjung anovelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities AT kimtaehoon anovelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities AT banerjeearaja novelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities AT kimyoonjung novelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities AT kimtaehoon novelvirusinducibleenhanceroftheinterferonbgenewithtightlylinkedpromoterandenhanceractivities |