International Immunology, Vol. 13, No. 5, 657-664,
May 2001
© 2001 Japanese Society for Immunology
A site in the complement receptor 2 (CR2/CD21) silencer is necessary for lineage specific transcriptional regulation
1 Departments of Immunology and
2 Medicine, Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
3 Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA
Correspondence to: V. M. Holers, Division of Rheumatology, Box B-115, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
Expression of human complement receptor type 2 (CR2/CD21) is primarily restricted to mature B cells and follicular dendritic cells. We previously described an intronic transcriptional silencer that controls the appropriate B cell-specific and developmentally restricted expression of human CR2/CD21 in both stably transfected cell lines and transgenic mice. Here we report the identification of a nucleotide sequence within the 2.5 kb CR2 silencer (CRS) that is crucial to its silencer function. This site comprises a binding site for the transcriptional repressor CBF1 (RBP-J or RBP-J
) as well as Sp1 and other as yet uncharacterized proteins. A 2-bp mutation which eliminates the binding of CBF1 and other protein(s) in vitro results in loss of silencer activity in vivo. These results demonstrate the importance of this site in regulating CR2 expression and suggest that CBF1, a component of the developmentally important Notch signaling pathway, may play a role in the control of human CR2 gene expression.
Keywords: B lymphocytes, CBF1, cellular differentiation, complement, gene regulation, transcription factors
4 Present address: Department of Immunology, Box 357650, University of Washington, Seattle, WA 98195, USA
Transmitting editor: L. H. Glimcher
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