SPECIFIC RECOGNITION OF THE BLK PROMOTER BY THE B-LYMPHOID TRANSCRIPTION FACTOR B-CELL-SPECIFIC ACTIVATOR PROTEIN

Several genes of the src family encode protein-tyrosine kinases that a ssociate with the B-cell antigen receptor complex and are activated up on receptor cross-linking, including blk, lyn, and fyn. The blk gene i s the only member of this family whose expression is restricted to B-l ymphhoid cells. In the B lineage, blk is developmentally regulated: bl k transcripts are first detected in pro-B-cells and persist until the differentiation of mature B-cells to plasma cells. We have found that the blk promoter is a target for a specific DNA-binding protein whose activity in B-lymphoid cell lines is positively correlated with blk ex pression. By three criteria, we have identified this DNA-binding prote in as the transcription factor B-cell-specific activator protein (BSAP ): 1) oligonucleotides containing known BSAP recognition sites were fo und to compete specifically with blk for binding to the protein detect ed in B-lymphoid extracts; 2) authentic BSAP was shown to bind the sam e site within the blk promoter as the protein identified in B-lymphoid extracts; and 3) the specific DNA-protein complex formed in B-lymphoi d extracts was shown to react with an anti-BSAP antiserum. BSAP has be en implicated previously in the transcriptional regulation of CD19, wh ose pattern of expression in B-cell development coincides with that of blk. These observations, and the correlation between expression of BS AP and expression of blk, suggest that BSAP is a positive regulator of blk transcription.