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

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

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS FUNCTIONAL REGULATION OF AN ANCESTRAL RAG TRANSPOSON _PROTORAG_ BY A _TRANS_-ACTING FACTOR YY1 IN LANCELET Article Open access

09 September 2020 ENDOGENOUS RETROVIRUSES ARE A SOURCE OF ENHANCERS WITH ONCOGENIC POTENTIAL IN ACUTE MYELOID LEUKAEMIA Article Open access 14 July 2020 THE TY1 RETROTRANSPOSON HARBORS A

DNA REGION THAT PERFORMS DUAL FUNCTIONS AS BOTH A GENE SILENCING AND CHROMATIN INSULATOR Article Open access 18 July 2024 ACCESSION CODES ACCESSIONS GENBANK/EMBL/DDBJ * AY215076 REFERENCES *

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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.). AUTHOR INFORMATION Author notes * Ziva Misulovin Present

address: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, 63110, USA * Wong Yu & Nikolaus Rajewsky Present address: Department of Biology, New York

University, Washington Square, New York, New York, 10003-6688, USA * Bernardo R Peixoto Present address: Molecular Genetic and Pathology Unit, Hospital Divino Espirito Santo, 9500, Azores,

Portugal AUTHORS AND AFFILIATIONS * Laboratory of Molecular Immunology, Rockefeller University, New York, 10021, New York, USA Nikos Yannoutsos, Ziva Misulovin, Anna Gazumyan, Wong Yu, 

Bernardo R Peixoto, Thomas Eisenreich & Michel C Nussenzweig * Howard Hughes Medical Institute, Rockefeller University, New York, 10021, New York, USA Vasco Barreto, Ziva Misulovin, Anna

Gazumyan, Thomas Eisenreich & Michel C Nussenzweig * Center of Studies in Physics and Biology, Rockefeller University, New York, 10021, New York, USA Nikolaus Rajewsky * Stanford

University Medical School, Stanford, California, 94305-5323, USA Wong Yu Authors * Nikos Yannoutsos View author publications You can also search for this author inPubMed Google Scholar *

Vasco Barreto View author publications You can also search for this author inPubMed Google Scholar * Ziva Misulovin View author publications You can also search for this author inPubMed 

Google Scholar * Anna Gazumyan View author publications You can also search for this author inPubMed Google Scholar * Wong Yu View author publications You can also search for this author

inPubMed Google Scholar * Nikolaus Rajewsky View author publications You can also search for this author inPubMed Google Scholar * Bernardo R Peixoto View author publications You can also

search for this author inPubMed Google Scholar * Thomas Eisenreich View author publications You can also search for this author inPubMed Google Scholar * Michel C Nussenzweig View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Nikos Yannoutsos or Michel C Nussenzweig. ETHICS DECLARATIONS COMPETING

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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 Download citation * Received: 06 January 2004 * Accepted: 22 January 2004 * Published: 14 March 2004 * Issue Date: 01 April 2004 * DOI:

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