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




Journal Title

Journal ISSN

Volume Title




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-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.


Supplementary data available at DOI.


Interferon, beta 1 (ifnb1), Chromatin, Gene regulation, Epigenetics, Luciferases


National 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].


CC BY 4.0 (Attribution), ©2014 The Authors