Abstract
We have identified a silencer and an antisilencing element that interact at a distance of 85 kilobases to regulate expression of the recombination activating genes Rag1 and Rag2 in thymocytes. Transgenic experiments showed that Rag promoter-proximal cis elements directed tissue-specific expression and that a Runx-dependent intergenic silencer suppressed expression in developing T cells. Deletion of the antisilencing element from the genomic Rag locus unmasked the intergenic silencer and abrogated Rag expression in developing CD4+CD8+ T cells. We speculate that the Rag antisilencing element belongs to a class of cis elements that might be useful for genome diversification by activating genes encoded by otherwise silent transposable elements.
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Acknowledgements
We thank K. Velinzon for flow cytometry cell sorting; members of the Nussenzweig laboratory and D. Dorsett for discussions; E. Besmer for help with the manuscript, and M. Zavolan for discussions and help with customizing SMASH; and D. Kioussis for the CD2 cassette. Supported in part by National Institutes of Health and Howard Hughes Medical Institute (M.C.N.).
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Yannoutsos, N., Barreto, V., Misulovin, Z. et al. A cis element in the recombination activating gene locus regulates gene expression by counteracting a distant silencer. Nat Immunol 5, 443–450 (2004). https://doi.org/10.1038/ni1053
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DOI: https://doi.org/10.1038/ni1053
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