Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells.

The recombination activating gene-1 (RAG-1) and RAG-2 are expressed specifically in immature lymphoid cells undergoing the recombination of antigen receptor genes. The regulation of murine RAG-2 promoter was studied and it was revealed that the -41/-17 RAG-2 promoter region, which is conserved between humans and mice, was indispensable for the ...
RAG-2 promoter activity in B-cell lines. The region contained 2 cis elements that bound c-Myb and Pax-5. Mutation in the c-Myb-binding site in the promoter reduced the promoter activity in B-cell lines. Cooperative activation of the RAG-2 promoter was seen by a combination of c-Myb and Pax-5 in a human embryonic kidney cell line (293T), via their synergistic DNA-binding. Deletion experiments showed that the C-terminus of c-Myb was responsible for their interaction. Furthermore, the dominant-negative c-Myb mutant suppressed the activation of the RAG-2 promoter in a pre-B-cell line as well as in 293T cells. These results suggest that cooperative binding of c-Myb and Pax-5 to the RAG-2 promoter is one of the mechanisms to direct the restricted expression of the RAG-2 in immature B cells.
Mesh Terms:
Animals, B-Cell-Specific Activator Protein, B-Lymphocyte Subsets, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Gene Expression Regulation, Gene Targeting, Genes, Dominant, Genes, myb, Humans, Kidney, Macromolecular Substances, Mice, Nuclear Proteins, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Proteins c-myb, Recombinant Fusion Proteins, Sequence Deletion, Sequence Homology, Amino Acid, Species Specificity, Structure-Activity Relationship, Transcription Factors, Transcription, Genetic, Transfection
Blood
Date: Jan. 15, 2002
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