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Roles for Transcription Factors Sp1, NF-kappa B, IRF3, and IRF7 in Expression of the Human IFNL4 Gene

Chinnaswamy, Sreedhar and Bhushan, Anand and Behera, Amit K and Ghosh, Sumona and Rampurkar, Vijay and Chandra, Vikas and Pandit, Bhaswati and Kundu, Tapas K (2016) Roles for Transcription Factors Sp1, NF-kappa B, IRF3, and IRF7 in Expression of the Human IFNL4 Gene. In: VIRAL IMMUNOLOGY, 29 (1). pp. 49-63.

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Official URL: http://dx.doi.org/10.1089/vim.2015.0076


The expression of a biologically active human IFN4 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 IFN4, 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-B), IFN regulatory factor 3 (IRF3), and IRF7. Interestingly, we also observe that overexpression of IFN4 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.

Item Type: Journal Article
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Additional Information: Copy right for this article belongs to the MARY ANN LIEBERT, INC, 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
Department/Centre: Others
Date Deposited: 10 Feb 2016 05:50
Last Modified: 10 Feb 2016 05:50
URI: http://eprints.iisc.ernet.in/id/eprint/53204

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