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

Reed NP, Henderson MA, Oltz EM, Aune TM
Genes Immun. 2013 14 (1): 7-12

PMID: 23076336 · PMCID: PMC4028662 · DOI:10.1038/gene.2012.47

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.

MeSH Terms (12)

Animals DNA-Binding Proteins Gene Expression Regulation Homeodomain Proteins Mice Mice, Inbred BALB C Repressor Proteins Thymocytes Trans-Activators Transcription, Genetic Transcriptional Activation Zinc Fingers

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