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A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription

Abstract

Interferon-gamma (IFN-γ) is an important cytokine that regulates cellular immune responses to intracellular pathogens and neoplasia. Regulation of IFN-γ expression is stringently controlled at the transcriptional level. In this report we describe two novel single nucleotide polymorphisms (SNPs); one, at −179 in the promoter, occurs in 4% of African Americans. This SNP represents a guanidine to thymidine transition and creates a potential AP-1 binding element. Electrophoretic mobility shift analysis reveals a unique complex binding to an oligonucleotide containing the variant −179T but not to the −179G using nuclear extracts from human peripheral blood T cells. In reporter gene assays, T cell lines transfected with the variant −204(179T) IFN-γ promoter show a six to 13-fold induction of luciferase activity in response to TNF-α over the common −204(179G) construct. The −179T allele identified in the proximal IFN-γ promoter confers TNF-α inducibility and may prove important in human immune disorders and responsiveness to pathogens.

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Acknowledgements

Special thanks to Dr Michael J Lenardo for providing the p80 Jurkat cell line, Dr Nancy H Colburn for helpful discussions, and Connie Champion and Susan Charbonneau for editorial assistance.

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Correspondence to H A Young.

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The publisher or recipient acknowledges the right of the US Government to retain a non-exclusive, royalty-free license in and to any copyright covering the article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health under Contract No. N01-CO-12400.

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Bream, J., Ping, A., Zhang, X. et al. A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription. Genes Immun 3, 165–169 (2002). https://doi.org/10.1038/sj.gene.6363870

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