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.