| Although the products of the RAG1 and RAG2 genes play an essential role in V(D)J recombination, the mechanisms responsible for the lymphoid- and developmental stage-specific expression of these two genes are poorly understood. We used a stable transfection assay to identify 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. The impairment in B cell development is due to decreased RAG transcript levels in developing B cells. We found that E2A transcription factors bind to E rag in vivo and can transactivate Erag-dependent reporter constructs in co-transfected 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. |
