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Characterization of KIR intermediate promoters reveals four promoter types associated with distinct expression patterns of KIR subtypes

Genes & Immunity volume 17, pages 66–74 (2016)Cite this article

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Abstract

The human killer cell immunoglobulin-like receptor (KIR) genes contain multiple promoters that control the process of gene activation and variegated expression of KIR on natural killer (NK) and T cells. Specific subfamilies of KIR genes have differences in the timing and tissue specificity of expression: however, previous studies of the proximal KIR promoters have not shown significant differences in activity between differentially expressed KIR gene subsets. The recent identification of an intermediate KIR promoter (ProI) associated with KIR2DL1 expression suggested a central role for this element in KIR expression. The current study identifies ProI elements in all of the KIR genes, revealing four classes of ProI that correspond with four distinct expression phenotypes of KIR subgroups: KIR2DL2/S2/L3 that are expressed early in reconstituting NK after transplant; KIR2DL4 that is expressed by CD56-bright NK in a non-variegated manner; KIR3DL3 that is not expressed by circulating NK cells; and the remaining KIR that are expressed by subsets of CD56-dim NK. The four classes of ProI are structurally diverse and display distinct functional properties. Altogether, these results indicate that KIR ProI elements contribute to the tissue/cell-type specificity of KIR transcription and cooperate with the probabilistic proximal promoter to control KIR expression.

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Acknowledgements

This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI), NIH, under contract HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. 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.

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Authors and Affiliations

  1. Basic Science Program, Leidos Biomedical Research Inc., Frederick National Lab, Frederick, MD, USA

    H Li, P W Wright & S K Anderson

  2. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA

    H Li, P W Wright, M McCullen & S K Anderson

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  1. H Li
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  2. P W Wright
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  3. M McCullen
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Correspondence to S K Anderson.

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Li, H., Wright, P., McCullen, M. et al. Characterization of KIR intermediate promoters reveals four promoter types associated with distinct expression patterns of KIR subtypes. Genes Immun 17, 66–74 (2016). https://doi.org/10.1038/gene.2015.56

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