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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jun 1;90(11):5364–5368. doi: 10.1073/pnas.90.11.5364

Identification of cell-specific and developmentally regulated nuclear factors that direct myeloid and lymphoid expression of the CD11a gene.

C S Shelley 1, O C Farokhzad 1, M A Arnaout 1
PMCID: PMC46717  PMID: 8099450

Abstract

Human CD11a/CD18 is a noncovalently associated heterodimeric receptor expressed exclusively on the surface of lymphocytes and myeloid cells. To begin to understand the mechanisms that direct the expression of the genes encoding this receptor, we have cloned and characterized the promoter region of the CD11a gene and localized cis-acting elements involved in its expression in lymphoid and myeloid cells. One such element is the "LYM" box, which interacts with two sets of DNA-binding activities, one primarily expressed in lymphocytes and preerythroid cells and the other expressed predominantly in myeloid cells. A second element required for expression of the CD11a gene contains the "GAGA" sequence RRRGAGGAAG (R indicates a purine), which interacts with the DNA-binding activities MS-1 and MS-2. MS-1 is expressed exclusively in myeloid cells and probably represents a member of the Ets family of transcription activators. MS-2 is present in epithelial, preerythroid, and lymphoid cells but is only detected in myeloid cells after differentiation. MS-2 also binds to a second element within the CD11a promoter and homologous elements present in the promoter regions of the CD11b and CD43 genes. Since MS-2 interacts with a number of different gene promoters and is developmentally regulated in myeloid cells, it may play a major role in regulating myeloid gene expression.

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Selected References

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  1. Agura E. D., Howard M., Collins S. J. Identification and sequence analysis of the promoter for the leukocyte integrin beta-subunit (CD18): a retinoic acid-inducible gene. Blood. 1992 Feb 1;79(3):602–609. [PubMed] [Google Scholar]
  2. Arnaout M. A. Leukocyte adhesion molecules deficiency: its structural basis, pathophysiology and implications for modulating the inflammatory response. Immunol Rev. 1990 Apr;114:145–180. doi: 10.1111/j.1600-065x.1990.tb00564.x. [DOI] [PubMed] [Google Scholar]
  3. Arnaout M. A., Spits H., Terhorst C., Pitt J., Todd R. F., 3rd Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo1 deficiency. Effects of cell activation on Mo1/LFA-1 surface expression in normal and deficient leukocytes. J Clin Invest. 1984 Oct;74(4):1291–1300. doi: 10.1172/JCI111539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arnaout M. A. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990 Mar 1;75(5):1037–1050. [PubMed] [Google Scholar]
  5. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  6. Borgmeyer U., Nowock J., Sippel A. E. The TGGCA-binding protein: a eukaryotic nuclear protein recognizing a symmetrical sequence on double-stranded linear DNA. Nucleic Acids Res. 1984 May 25;12(10):4295–4311. doi: 10.1093/nar/12.10.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Carlos T. M., Harlan J. M. Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev. 1990 Apr;114:5–28. doi: 10.1111/j.1600-065x.1990.tb00559.x. [DOI] [PubMed] [Google Scholar]
  9. Chow B. K., Ting V., Tufaro F., MacGillivray R. T. Characterization of a novel liver-specific enhancer in the human prothrombin gene. J Biol Chem. 1991 Oct 5;266(28):18927–18933. [PubMed] [Google Scholar]
  10. Clark B. D., Collins K. L., Gandy M. S., Webb A. C., Auron P. E. Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. Nucleic Acids Res. 1986 Oct 24;14(20):7897–7914. doi: 10.1093/nar/14.20.7897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Corbi A. L., Larson R. S., Kishimoto T. K., Springer T. A., Morton C. C. Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion. J Exp Med. 1988 May 1;167(5):1597–1607. doi: 10.1084/jem.167.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans T., Reitman M., Felsenfeld G. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976–5980. doi: 10.1073/pnas.85.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hogge D. E., Misawa S., Parsa N. Z., Pollak A., Testa J. R. Abnormalities of chromosome 16 in association with acute myelomonocytic leukemia and dysplastic bone marrow eosinophils. J Clin Oncol. 1984 Jun;2(6):550–557. doi: 10.1200/JCO.1984.2.6.550. [DOI] [PubMed] [Google Scholar]
  15. Hohn P. A., Popescu N. C., Hanson R. D., Salvesen G., Ley T. J. Genomic organization and chromosomal localization of the human cathepsin G gene. J Biol Chem. 1989 Aug 15;264(23):13412–13419. [PubMed] [Google Scholar]
  16. Huhtala P., Tuuttila A., Chow L. T., Lohi J., Keski-Oja J., Tryggvason K. Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem. 1991 Sep 5;266(25):16485–16490. [PubMed] [Google Scholar]
  17. Johnson A. C., Jinno Y., Merlino G. T. Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. Mol Cell Biol. 1988 Oct;8(10):4174–4184. doi: 10.1128/mcb.8.10.4174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karim F. D., Urness L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. A. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990 Sep;4(9):1451–1453. doi: 10.1101/gad.4.9.1451. [DOI] [PubMed] [Google Scholar]
  19. Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. doi: 10.1016/0092-8674(90)90219-5. [DOI] [PubMed] [Google Scholar]
  20. Kudo S., Fukuda M. A short, novel promoter sequence confers the expression of human leukosialin, a major sialoglycoprotein on leukocytes. J Biol Chem. 1991 May 5;266(13):8483–8489. [PubMed] [Google Scholar]
  21. Lagasse E., Clerc R. G. Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation. Mol Cell Biol. 1988 Jun;8(6):2402–2410. doi: 10.1128/mcb.8.6.2402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Larson R. S., Corbi A. L., Berman L., Springer T. Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily. J Cell Biol. 1989 Feb;108(2):703–712. doi: 10.1083/jcb.108.2.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Le Beau M. M., Larson R. A., Bitter M. A., Vardiman J. W., Golomb H. M., Rowley J. D. Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. N Engl J Med. 1983 Sep 15;309(11):630–636. doi: 10.1056/NEJM198309153091103. [DOI] [PubMed] [Google Scholar]
  24. Miller L. J., Schwarting R., Springer T. A. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J Immunol. 1986 Nov 1;137(9):2891–2900. [PubMed] [Google Scholar]
  25. Morishita K., Tsuchiya M., Asano S., Kaziro Y., Nagata S. Chromosomal gene structure of human myeloperoxidase and regulation of its expression by granulocyte colony-stimulating factor. J Biol Chem. 1987 Nov 5;262(31):15208–15213. [PubMed] [Google Scholar]
  26. Nimer S., Fraser J., Richards J., Lynch M., Gasson J. The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity. Mol Cell Biol. 1990 Nov;10(11):6084–6088. doi: 10.1128/mcb.10.11.6084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Orkin S. H. Globin gene regulation and switching: circa 1990. Cell. 1990 Nov 16;63(4):665–672. doi: 10.1016/0092-8674(90)90133-y. [DOI] [PubMed] [Google Scholar]
  28. Pearse R. N., Feinman R., Ravetch J. V. Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: transcriptional induction by gamma-interferon is mediated through common DNA response elements. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11305–11309. doi: 10.1073/pnas.88.24.11305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roebroek A. J., Schalken J. A., Bussemakers M. J., van Heerikhuizen H., Onnekink C., Debruyne F. M., Bloemers H. P., Van de Ven W. J. Characterization of human c-fes/fps reveals a new transcription unit (fur) in the immediately upstream region of the proto-oncogene. Mol Biol Rep. 1986;11(2):117–125. doi: 10.1007/BF00364823. [DOI] [PubMed] [Google Scholar]
  31. Rosen G. D., Birkenmeier T. M., Dean D. C. Characterization of the alpha 4 integrin gene promoter. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4094–4098. doi: 10.1073/pnas.88.10.4094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rupp R. A., Kruse U., Multhaup G., Göbel U., Beyreuther K., Sippel A. E. Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. Nucleic Acids Res. 1990 May 11;18(9):2607–2616. doi: 10.1093/nar/18.9.2607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Shapiro L. H., Ashmun R. A., Roberts W. M., Look A. T. Separate promoters control transcription of the human aminopeptidase N gene in myeloid and intestinal epithelial cells. J Biol Chem. 1991 Jun 25;266(18):11999–12007. [PubMed] [Google Scholar]
  36. Shelley C. S., Arnaout M. A. The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10525–10529. doi: 10.1073/pnas.88.23.10525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shelley C. S., Remold-O'Donnell E., Rosen F. S., Whitehead A. S. Structure of the human sialophorin (CD43) gene. Identification of features atypical of genes encoding integral membrane proteins. Biochem J. 1990 Sep 15;270(3):569–576. doi: 10.1042/bj2700569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Skalnik D. G., Strauss E. C., Orkin S. H. CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91-phox gene promoter. J Biol Chem. 1991 Sep 5;266(25):16736–16744. [PubMed] [Google Scholar]
  39. Takahashi H., Nukiwa T., Yoshimura K., Quick C. D., States D. J., Holmes M. D., Whang-Peng J., Knutsen T., Crystal R. G. Structure of the human neutrophil elastase gene. J Biol Chem. 1988 Oct 15;263(29):14739–14747. [PubMed] [Google Scholar]
  40. Wall L., deBoer E., Grosveld F. The human beta-globin gene 3' enhancer contains multiple binding sites for an erythroid-specific protein. Genes Dev. 1988 Sep;2(9):1089–1100. doi: 10.1101/gad.2.9.1089. [DOI] [PubMed] [Google Scholar]
  41. Wilson D. B., Dorfman D. M., Orkin S. H. A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol. 1990 Sep;10(9):4854–4862. doi: 10.1128/mcb.10.9.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wood W. M., Kao M. Y., Gordon D. F., Ridgway E. C. Thyroid hormone regulates the mouse thyrotropin beta-subunit gene promoter in transfected primary thyrotropes. J Biol Chem. 1989 Sep 5;264(25):14840–14847. [PubMed] [Google Scholar]

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