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 associate with the B-cell antigen receptor complex and are activated upon receptor cross-linking, including blk, lyn, and fyn. The blk gene is the only member of this family whose expression is restricted to B-lymphoid cells. In the B lineage, blk is developmentally regulated: blk 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 expression. By three criteria, we have identified this DNA-binding protein as the transcription factor B-cell-specific activator protein (BSAP): 1) oligonucleotides containing known BSAP recognition sites were found to compete specifically with blk for binding to the protein detected in B-lymphoid extracts; 2) authentic BSAP was shown to bind the same site within the blk promoter as the protein identified in B-lymphoid extracts; and 3) the specific DNA-protein complex formed in B-lymphoid extracts was shown to react with an anti-BSAP antiserum. BSAP has been implicated previously in the transcriptional regulation of CD19, whose pattern of expression in B-cell development coincides with that of blk. These observations, and the correlation between expression of BSAP and expression of blk, suggest that BSAP is a positive regulator of blk transcription.