A conserved transcriptional enhancer regulates RAG gene expression in developing B cells

Immunity. 2003 Jul;19(1):105-17. doi: 10.1016/s1074-7613(03)00181-x.


Although expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood. We have identified a novel, evolutionarily conserved transcriptional enhancer in the RAG locus, called Erag, which was essential for the expression of a chromosomal reporter gene driven by either RAG promoter. Targeted deletion of Erag in the mouse germline results in a partial block in B cell development associated with deficient V(D)J recombination, whereas T cell development appears unaffected. We found that E2A transcription factors bind to Erag in vivo and can transactivate Erag-dependent reporter constructs in cotransfected cell lines. These findings lead us to conclude that RAG transcription is regulated by distinct elements in developing B and T cells and that Erag is required for optimal levels of RAG expression in early B cell precursors but not in T cells.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cell Line
  • DNA Nucleotidyltransferases / physiology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic / physiology*
  • Gene Expression Regulation*
  • Genes, RAG-1*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Receptors, Antigen, B-Cell / physiology
  • Recombinases
  • Transcription Factors / metabolism
  • Transfection


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RAG2 protein, human
  • Rag2 protein, mouse
  • Receptors, Antigen, B-Cell
  • Recombinases
  • TCF3 protein, human
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • DNA Nucleotidyltransferases