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*
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
Complement receptor 2 (CR2) is regulated at the transcriptional
level, but the promoter elements and the transcription factors that
bind to them and contribute to its regulation are unknown. After
documenting that PMA and cAMP induced the activity of the CR2 promoter
by 10-fold, we conducted promoter truncation and mutagenesis
experiments, in conjunction with shift assays, to determine the
functionally important regions of the promoter and the proteins that
bind to them. We identified two regions, separated by 
900
nucleotides, which together were responsible for inducible promoter
activity. Mutagenesis of single promoter elements demonstrated a
functional upstream stimulatory factor/E box in the TATA box-proximal
region and three equally important, closely spaced, CREB/AP-1
half-sites in the upstream promoter region. The cAMP response
element-binding protein (CREB)/AP-1 half-sites bound in vitro Jun and
CREB that are induced by protein kinases A and/or C. The 900-nucleotide
segment stretching between the above two regions had no functional
impact on the induced transcription, and its deletion increased the
promoter activity. Finally, a region upstream of the distal site had a
repressor activity on CR2 transcription. Moreover, IL-4 induced binding
of CREB and AP-1 to the upstream promoter elements and resulted in
increased CR2 surface protein expression. These studies have
characterized regions of the CR2 promoter and the transcription factors
that bind to them and are crucial to induced CR2 expression. Our
studies may provide insights to novel approaches to modulate B cell
function by regulating CR2 gene
transcription.
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