title: A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520, USA.
authors.forename: A Raja
authors.initials: AR
authors.lastname: Banerjee
authors.affiliation: Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA genome@utdallas.edu.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis; D029082:Sendai virus / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D014157:Transcription Factors; D012313:RNA; D016899:Interferon-beta