Distinct Factors Regulate the Murine RAG-2 Promoter in B- and T-Cell Lines

AUTOR(ES)

Lauring, Josh

FONTE

American Society for Microbiology

RESUMO

The recombination activating genes RAG-1 and RAG-2 are expressed in a lymphoid-cell-specific and developmentally regulated fashion. To understand the transcriptional basis for this regulation, we have cloned and characterized the murine RAG-2 promoter. The promoter was lymphoid cell specific, showing activity in various B- and T-cell lines but little activity in nonlymphoid cells. To our surprise, however, the promoter was regulated differently in B and T cells. Using nuclear extracts from B-cell lines, we found that the B-cell-specific transcription factor BSAP (Pax-5) could bind to a conserved sequence critical for promoter activity. BSAP activated the promoter in transfected cells, and the BSAP site was occupied in a tissue-specific manner in vivo. An overlapping DNA sequence binding to a distinct factor was necessary for promoter activity in T cells. Full promoter activity in T cells was also dependent on a more distal DNA sequence whose disruption had no effect on B-cell activity. The unexpected finding that a B-cell-specific factor regulates the RAG-2 promoter may explain some of the recently observed differences in the regulation of RAG transcription between B and T cells.

Documentos Relacionados

• Evidence for different interleukin 1 receptors in murine B- and T-cell lines.
• Entrance and survival of Salmonella typhimurium and Yersinia enterocolitica within human B- and T-cell lines.
• RAG-1 and RAG-2 are not sufficient to direct all phases of immunoglobulin gene rearrangement in pre-B-cell lines.
• Proliferation and differentiation of single hapten-specific B lymphocytes is promoted by T-cell factor(s) distinct from T-cell growth factor.
• Adenosine deaminase activity in chronic lymphocytic leukemia. Relationship to B- and T-cell subpopulations.