Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1992 Jun;12(6):2662–2672. doi: 10.1128/mcb.12.6.2662

The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.

Z Kozmik 1, S Wang 1, P Dörfler 1, B Adams 1, M Busslinger 1
PMCID: PMC364460  PMID: 1375324

Abstract

The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.

Full text

PDF
2662

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barberis A., Superti-Furga G., Busslinger M. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell. 1987 Jul 31;50(3):347–359. doi: 10.1016/0092-8674(87)90489-2. [DOI] [PubMed] [Google Scholar]
  2. Barberis A., Superti-Furga G., Vitelli L., Kemler I., Busslinger M. Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin. Genes Dev. 1989 May;3(5):663–675. doi: 10.1101/gad.3.5.663. [DOI] [PubMed] [Google Scholar]
  3. Barberis A., Widenhorn K., Vitelli L., Busslinger M. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Genes Dev. 1990 May;4(5):849–859. doi: 10.1101/gad.4.5.849. [DOI] [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Busslinger M., Moschonas N., Flavell R. A. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron. Cell. 1981 Dec;27(2 Pt 1):289–298. doi: 10.1016/0092-8674(81)90412-8. [DOI] [PubMed] [Google Scholar]
  6. Chen W., Struhl K. Yeast upstream activator protein GCN4 can stimulate transcription when its binding site replaces the TATA element. EMBO J. 1989 Jan;8(1):261–268. doi: 10.1002/j.1460-2075.1989.tb03372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ehrich E., Craig A., Poustka A., Frischauf A. M., Lehrach H. A family of cosmid vectors with the multi-copy R6K replication origin. Gene. 1987;57(2-3):229–237. doi: 10.1016/0378-1119(87)90126-0. [DOI] [PubMed] [Google Scholar]
  8. Fors L., Saavedra R. A., Hood L. Cloning of the shark Po promoter using a genomic walking technique based on the polymerase chain reaction. Nucleic Acids Res. 1990 May 11;18(9):2793–2799. doi: 10.1093/nar/18.9.2793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Golay J. T., Crawford D. H. Pathways of human B-lymphocyte activation blocked by B-cell specific monoclonal antibodies. Immunology. 1987 Oct;62(2):279–284. [PMC free article] [PubMed] [Google Scholar]
  11. Grosschedl R., Birnstiel M. L. Identification of regulatory sequences in the prelude sequences of an H2A histone gene by the study of specific deletion mutants in vivo. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1432–1436. doi: 10.1073/pnas.77.3.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hagman J., Travis A., Grosschedl R. A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. EMBO J. 1991 Nov;10(11):3409–3417. doi: 10.1002/j.1460-2075.1991.tb04905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hebell T., Ahearn J. M., Fearon D. T. Suppression of the immune response by a soluble complement receptor of B lymphocytes. Science. 1991 Oct 4;254(5028):102–105. doi: 10.1126/science.1718035. [DOI] [PubMed] [Google Scholar]
  14. Hermanson G. G., Briskin M., Sigman D., Wall R. Immunoglobulin enhancer and promoter motifs 5' of the B29 B-cell-specific gene. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7341–7345. doi: 10.1073/pnas.86.19.7341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kozmík Z., Paces V. Multiple bandshift assay: rapid identification and cloning of DNA fragments containing specific protein-binding sites. Gene. 1990 Jun 15;90(2):287–291. doi: 10.1016/0378-1119(90)90192-t. [DOI] [PubMed] [Google Scholar]
  16. Ledbetter J. A., Rabinovitch P. S., June C. H., Song C. W., Clark E. A., Uckun F. M. Antigen-independent regulation of cytoplasmic calcium in B cells with a 12-kDa B-cell growth factor and anti-CD19. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1897–1901. doi: 10.1073/pnas.85.6.1897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee K. H., Kinashi T., Tohyama K., Tashiro K., Funato N., Hama K., Honjo T. Different stromal cell lines support lineage-selective differentiation of the multipotential bone marrow stem cell clone LyD9. J Exp Med. 1991 May 1;173(5):1257–1266. doi: 10.1084/jem.173.5.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsumoto A. K., Kopicky-Burd J., Carter R. H., Tuveson D. A., Tedder T. F., Fearon D. T. Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. J Exp Med. 1991 Jan 1;173(1):55–64. doi: 10.1084/jem.173.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mueller P. R., Wold B. In vivo footprinting of a muscle specific enhancer by ligation mediated PCR. Science. 1989 Nov 10;246(4931):780–786. doi: 10.1126/science.2814500. [DOI] [PubMed] [Google Scholar]
  20. Nadler L. M., Anderson K. C., Marti G., Bates M., Park E., Daley J. F., Schlossman S. F. B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol. 1983 Jul;131(1):244–250. [PubMed] [Google Scholar]
  21. Nakayama E., von Hoegen I., Parnes J. R. Sequence of the Lyb-2 B-cell differentiation antigen defines a gene superfamily of receptors with inverted membrane orientation. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1352–1356. doi: 10.1073/pnas.86.4.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palacios R., Karasuyama H., Rolink A. Ly1+ PRO-B lymphocyte clones. Phenotype, growth requirements and differentiation in vitro and in vivo. EMBO J. 1987 Dec 1;6(12):3687–3693. doi: 10.1002/j.1460-2075.1987.tb02702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Petterson M., Schaffner W. A purine-rich DNA sequence motif present in SV40 and lymphotropic papovavirus binds a lymphoid-specific factor and contributes to enhancer activity in lymphoid cells. Genes Dev. 1987 Nov;1(9):962–972. doi: 10.1101/gad.1.9.962. [DOI] [PubMed] [Google Scholar]
  24. Pezzutto A., Dörken B., Rabinovitch P. S., Ledbetter J. A., Moldenhauer G., Clark E. A. CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J Immunol. 1987 May 1;138(9):2793–2799. [PubMed] [Google Scholar]
  25. Pugh B. F., Tjian R. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell. 1990 Jun 29;61(7):1187–1197. doi: 10.1016/0092-8674(90)90683-6. [DOI] [PubMed] [Google Scholar]
  26. Rolink A., Melchers F. Molecular and cellular origins of B lymphocyte diversity. Cell. 1991 Sep 20;66(6):1081–1094. doi: 10.1016/0092-8674(91)90032-t. [DOI] [PubMed] [Google Scholar]
  27. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Siebenlist U., Simpson R. B., Gilbert W. E. coli RNA polymerase interacts homologously with two different promoters. Cell. 1980 Jun;20(2):269–281. doi: 10.1016/0092-8674(80)90613-3. [DOI] [PubMed] [Google Scholar]
  30. Stamenkovic I., Seed B. CD19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr virus-related cytoplasmic tail. J Exp Med. 1988 Sep 1;168(3):1205–1210. doi: 10.1084/jem.168.3.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tedder T. F., Isaacs C. M. Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes. A new member of the immunoglobulin superfamily. J Immunol. 1989 Jul 15;143(2):712–717. [PubMed] [Google Scholar]
  32. Uckun F. M., Jaszcz W., Ambrus J. L., Fauci A. S., Gajl-Peczalska K., Song C. W., Wick M. R., Myers D. E., Waddick K., Ledbetter J. A. Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins. Blood. 1988 Jan;71(1):13–29. [PubMed] [Google Scholar]
  33. Vitelli L., Kemler I., Lauber B., Birnstiel M. L., Busslinger M. Developmental regulation of micro-injected histone genes in sea urchin embryos. Dev Biol. 1988 May;127(1):54–63. doi: 10.1016/0012-1606(88)90188-1. [DOI] [PubMed] [Google Scholar]
  34. Westin G., Gerster T., Müller M. M., Schaffner G., Schaffner W. OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Res. 1987 Sep 11;15(17):6787–6798. doi: 10.1093/nar/15.17.6787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zhou L. J., Ord D. C., Hughes A. L., Tedder T. F. Structure and domain organization of the CD19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain. J Immunol. 1991 Aug 15;147(4):1424–1432. [PubMed] [Google Scholar]
  36. de Rie M. A., Schumacher T. N., van Schijndel G. M., van Lier R. A., Miedema F. Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol. 1989 Feb;118(2):368–381. doi: 10.1016/0008-8749(89)90385-7. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES