Nature Immunology
5, 443 - 450 (2004)
Published online: 14 March 2004; | doi:10.1038/ni1053
A cis element in the recombination activating gene locus regulates gene expression by counteracting a distant silencerNikos Yannoutsos1, Vasco Barreto2, Ziva Misulovin1, 2, 4, Anna Gazumyan1, 2, Wong Yu1, 4, Nikolaus Rajewsky3, 4, Bernardo R Peixoto1, 4, Thomas Eisenreich1, 2
& Michel C Nussenzweig1, 21
Laboratory of Molecular Immunology, Rockefeller University, New York, New York
10021, USA. 2
Howard Hughes Medical Institute, Rockefeller University, New York, New York
10021, USA. 3
Center of Studies in Physics and Biology, Rockefeller University, New York, New York
10021, USA. 4
Present addresses: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
63110, USA (Z.M.), Stanford University Medical School, Stanford, California
94305-5323, USA (W.Y.), New York University, Department of Biology, Washington Square, New York, New York
10003-6688, USA (N.R.), and Molecular Genetic and Pathology Unit, Hospital Divino Espirito Santo, 9500
Azores-Portugal (B.R.P.).
Correspondence should be addressed to Nikos Yannoutsos yannoun@rockvax.rockefeller.edu or Michel C Nussenzweig nussen@mail.rockefeller.eduWe 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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