A Novel Virus-Inducible Enhancer of the Interferon-β Gene with Tightly Linked Promoter and Enhancer Activities

dc.contributor.authorBanerjee, A. Rajaen_US
dc.contributor.authorKim, Yoon Jungen_US
dc.contributor.authorKim, Tae Hoonen_US
dc.contributor.utdAuthorKim, Yoon Jungen_US
dc.contributor.utdAuthorKim, Tae Hoonen_US
dc.date.accessioned2015-03-25T21:58:41Z
dc.date.available2015-03-25T21:58:41Z
dc.date.created2014-10-27en_US
dc.date.issued2014-10-27en_US
dc.descriptionSupplementary data available at DOI.en_US
dc.description.abstractLong-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-beta 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-beta. 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.en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases [R21AI107067]; National Cancer Institute [R01CA140485]; National Institutes of Health Training Grant [T32M007499]. Funding for open access charge: National Institute of Allergy and Infectious Diseases [R21AI107067].en_US
dc.identifier.bibliographicCitationBanerjee, A. Raja, Yoon Jung Kim, and Tae Hoon Kim. 2014. "A novel virus-inducible enhancer of the interferon-beta gene with tightly linked promoter and enhancer activities." Nucleic Acids Research 42(20): doi:10.1093/nar/gku1018.en_US
dc.identifier.issn0305-1048en_US
dc.identifier.issue20en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/4379
dc.identifier.volume42en_US
dc.relation.urihttp://dx.doi.org/10.1093/nar/gku1018
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2014 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNucleic Acids Research
dc.subjectInterferon, beta 1 (ifnb1)en_US
dc.subjectChromatinen_US
dc.subjectGene regulationen_US
dc.subjectEpigeneticsen_US
dc.subjectLuciferasesen_US
dc.titleA Novel Virus-Inducible Enhancer of the Interferon-β Gene with Tightly Linked Promoter and Enhancer Activitiesen_US
dc.type.genreArticleen_US

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