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

Cellular & Molecular Immunology volume 13, pages 119–131 (2016)Cite this article

Abstract

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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Acknowledgements

This study was generously supported by the National Health and Medical Research Council of Australia (303206 to DU and LJA), the Lupus Research Institute (to SAB), the Alliance for Lupus Research (to SAB, DU and BPT), National Institutes of Health (R01AI070983 to SAB, DU and BPT, K24 AI078004 to SAB, and P01AI083194, P01AR049084, R37AI024717 and U01HG006828 to JBH) and the US Department of Veterans Affairs (to JBH). The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia

    Rhonda L Taylor, Han Leng Ng, Lawrence J Abraham & Daniela Ulgiati

  2. Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia

    Rhonda L Taylor, Mahdad Karimi & Elizabeth Quail

  3. Telethon Kids Institute, The University of Western Australia, Crawley, WA, Australia

    Mark N Cruickshank

  4. Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    Kenneth M Kaufman & John B Harley

  5. US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA

    Kenneth M Kaufman & John B Harley

  6. Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Betty P Tsao

  7. Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA,

    Susan A Boackle

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  1. Rhonda L Taylor
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Correspondence to Daniela Ulgiati.

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Taylor, R., Cruickshank, M., Karimi, M. et al. Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells. Cell Mol Immunol 13, 119–131 (2016). https://doi.org/10.1038/cmi.2014.138

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