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. (Blood. 2002;99:576-583) (C) 2002 by The American Society of Hematology.