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The promoter and 5' flanking sequences controlling human B29 gene
expression
AA Thompson, WJ Wood , MJ Gilly, MA Damore, SA Omori and R Wall
Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Los
Angeles, CA, USA.
The product of the B-cell-specific B29 gene (B29, Ig beta, CD79b) is
essential for Ig-mediated B-cell activation via the B-cell antigen receptor
complex (BCR) on human and murine B lymphocytes. To better understand the
regulation of this pivotal gene, we have analyzed the human genomic DNA
sequence upstream of the B29 ATG start codon for transcriptional control
activity. The human B29 gene lacks either a TATA or a CAAT box and
transcription is initiated at multiple sites. The minimal promoter of the
human B29 gene is contained within a 193-bp region 5' of these multiple
start sites. This minimal promoter exhibits B-cell-specific activity and
contains SP1, ETS, OCT, and IKAROS/LYF-1 transcription factor motifs. All
these motifs are strikingly conserved in sequence 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 conserved sequence (BCS), found upstream of
both human and murine B29 promoters, appears to stimulate B29 transcription
through a novel mechanism. A single BCS had little effect either on the
minimal B29 promoter or on a heterologous promoter. Instead, the BCS
stimulated transcription by counteracting 5' negative regulatory DNA
sequences that block the activity of the B29 minimal promoter in its
absence. These findings indicate that B29 gene expression is controlled by
the complex interplay of positive and negative regulatory elements.
Volume 87,
Issue 2,
pp. 666-673,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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