title: Roles for Transcription Factors Sp1, NF-κB, IRF3, and IRF7 in Expression of the Human IFNL4 Gene.
abstract: The expression of a biologically active human IFNλ4 depends on the presence of a frameshift deletion polymorphism within the first exon of the interferon lambda 4 (IFNL4) gene. In this report, we use the lung carcinoma-derived cell line, A549, which is genetically viable to express a functional IFNλ4, to address transcriptional requirements of the IFNL4 gene. We show that the GC-rich DNA-binding transcription factor (TF) specificity protein 1 (Sp1) is recruited to the IFNL4 promoter and has a role in induction of gene expression upon stimulation with viral RNA mimic poly(I:C). By using RNAi and overexpression strategies, we also show key roles in IFNL4 gene expression for the virus-inducible TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), IFN regulatory factor 3 (IRF3), and IRF7. Interestingly, we also observe that overexpression of IFNλ4 influences IFNL4 promoter activity, which may further be dependent on the retinoic acid-inducible gene-I (RIG-I)-like receptor pathway. Together, our work for the first time reports on the functional characterization of the human IFNL4 promoter.
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Chinnaswamy
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Anand
authors.initials: A
authors.lastname: Bhushan
authors.affiliation: 2 Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Bangalore, India .
authors.forename: Amit K
authors.initials: AK
authors.lastname: Behera
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Sumona
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Vijay
authors.initials: V
authors.lastname: Rampurkar
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Vikas
authors.initials: V
authors.lastname: Chandra
authors.affiliation: 1 National Institute of Biomedical Genomics , Kalyani, West Bengal, India .
authors.forename: Bhaswati
authors.initials: B
authors.lastname: Pandit
authors.affiliation: 2 Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Bangalore, India .
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics*; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007378:Interleukins; D052002:NF-kappa B p50 Subunit; D011070:Poly I-C; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; D016329:Sp1 Transcription Factor; D051996:Transcription Factor RelA; C579163:IFNL4 protein, human; D000095022:Interferon Lambda; C494232:IRF3 protein, human; C494234:IRF7 protein, human; C437968:PLAAT4 protein, human; C498143:RELA protein, human; C108209:SP1 protein, human