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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Published in: | Immunity (Cambridge, Mass.) Vol. 19; no. 1; pp. 105 - 117 |
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Main Authors: | , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Elsevier Inc
01-07-2003
Elsevier Limited |
Subjects: | |
Online Access: | Get full text |
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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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/S1074-7613(03)00181-X |