A conserved transcriptional enhancer regulates RAG gene expression in developing B cells.
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.
Hsu
Lih-Yun
LY
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Lauring
Josh
J
Liang
Hong-Erh
HE
Greenbaum
Stephen
S
Cado
Dragana
D
Zhuang
Yuan
Y
Schlissel
Mark S
MS
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002460:Cell Line; D004254:DNA Nucleotidyltransferases / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D016654:Genes, RAG-1; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D045522:Recombinases; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004254:DNA Nucleotidyltransferases; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell; D045522:Recombinases; D014157:Transcription Factors; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C407909:TCF3 protein, human; C064655:V(D)J recombination activating protein 2