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Nat Immunol. 2004 Apr;5(4):443-50. Epub 2004 Mar 14.

A cis element in the recombination activating gene locus regulates gene expression by counteracting a distant silencer.

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Laboratory of Molecular Immunology, Rockefeller University, New York, New York 10021, USA.


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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