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Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609

Genes & Immunity volume 14, pages 7–12 (2013)Cite this article

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Abstract

Recombination-activating gene 1 (Rag1) and Rag2 enzymes are required for T cell receptor assembly and thymocyte development. The mechanisms underlying the transcriptional activation and repression of Rag1 and Rag2 are incompletely understood. The zinc-finger protein, Zfp608, represses Rag1 and Rag2 expression when expressed in thymocytes blocking T-cell maturation. Here we show that the related zinc-finger protein, Zfp609, is necessary for Rag1 and Rag2 expression in developing thymocytes. Zfp608 represses Rag1 and Rag2 expression indirectly by repressing the expression of Zfp609. Thus, the balance of Zfp608 and Zfp609 plays a critical role in regulating Rag1 and Rag2 expression, which may manifest itself not only during development of immature thymocytes into mature T cells but also in generation of the T-cell arm of the adaptive immune system, which does not fully develop until after birth.

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Acknowledgements

We thank John Tossberg, Chase Spurlock and Sarah Collier for scientific discussion and comments. Support was provided by grants from the National Institute of Allergy and Infectious Disease (AI 074945, AI 079732 and AI 044924) and the National Heart, Lung, and Blood Institute (T32HL094296).

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Authors and Affiliations

  1. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    N P Reed, M A Henderson & T M Aune

  2. Department of Pathology, Washington University School of Medicine, St Louis, MO, USA

    E M Oltz

  3. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA

    T M Aune

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  1. N P Reed
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  2. M A Henderson
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  3. E M Oltz
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  4. T M Aune
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Correspondence to T M Aune.

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Reed, N., Henderson, M., Oltz, E. et al. Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609. Genes Immun 14, 7–12 (2013). https://doi.org/10.1038/gene.2012.47

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