THE PROMOTER AND 5'-FLANKING SEQUENCES CONTROLLING HUMAN B29 GENE-EXPRESSION

The product of the B-cell-specific B29 gene (B29, Ig beta, CD79b) is e ssential for Ig-mediated B-cell activation via the B-cell antigen rece ptor complex (BCR) on human and murine B lymphocytes. To better unders tand the regulation of this pivotal gene, we have analyzed the human g enomic DNA sequence upstream of the B29 ATG start codon for transcript ional control activity. The human B29 gene lacks either a TATA or a CA AT box and transcription is initiated at multiple sites. The minimal p romoter of the human B29 gene is contained within a 193-bp region 5' o f these multiple start sites. This minimal promoter exhibits B-cell-sp ecific activity and contains SP1, ETS, OCT, and IKAROS/LYF-1 transcrip tion factor motifs. All these motifs are strikingly conserved in seque nce and placement relative to the previously characterized murine B29 promoter. Additional upstream gene segments dramatically affected B29 minimal promoter activity. A newly identified motif called the B29 con served sequence (BCS), found upstream of both human and murine B29 pro moters, appears to stimulate B29 transcription through a novel mechani sm. A single BCS had little effect either on the minimal B29 promoter or on a heterologous promoter. Instead, the BCS stimulated transcripti on by counteracting 5' negative regulatory DNA sequences that block th e activity of the B29 minimal promoter in its absence. These findings indicate that B29 gene expression is controlled by the complex interpl ay of positive and negative regulatory elements. (C) 1996 by The Ameri can Society of Hematology.