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

Nat Immunol. 2004 Apr;5(4):443-50. doi: 10.1038/ni1053. Epub 2004 Mar 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Gene Expression Regulation*
  • Genes, RAG-1*
  • Mice
  • Proto-Oncogene Proteins / metabolism
  • Sequence Deletion
  • Silencer Elements, Transcriptional*
  • Thymus Gland / metabolism*
  • Transcription Factors / metabolism


  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Rag2 protein, mouse
  • Runx1 protein, mouse
  • Transcription Factors
  • V(D)J recombination activating protein 2