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Cell Mol Immunol. 2016 Jan;13(1):119-31. doi: 10.1038/cmi.2014.138. Epub 2015 Feb 2.

Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells.

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School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia.
Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia.
Telethon Kids Institute, The University of Western Australia, Crawley, WA, Australia.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.


Complement receptor 2 (CR2/CD21) is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/CD21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.

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