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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Vol. 19; no. 1; pp. 105 - 117
Main Authors: Hsu, Lih-Yun, Lauring, Josh, Liang, Hong-Erh, Greenbaum, Stephen, Cado, Dragana, Zhuang, Yuan, Schlissel, Mark S.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-07-2003
Elsevier Limited
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Summary: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 E rag, which was essential for the expression of a chromosomal reporter gene driven by either RAG promoter. Targeted deletion of E rag 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 E rag in vivo and can transactivate E rag-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 E rag is required for optimal levels of RAG expression in early B cell precursors but not in T cells.
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ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(03)00181-X