Skip to main content
PMC home page
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
. 1995 Jan 31;92(3):801–805. doi: 10.1073/pnas.92.3.801

CD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity.

A G Rosmarin 1, D Caprio 1, R Levy 1, C Simkevich 1
PMCID: PMC42708  PMID: 7846055

Abstract

Normal cellular differentiation is linked to tightly regulated gene transcription. However, the DNA elements and trans-acting factors that regulate transcription in myeloid cells are poorly defined. CD18, the beta chain of the leukocyte integrins, is transcriptionally regulated during myeloid differentiation. The CD18 promoter is active after transfection into myeloid cells. We demonstrate that a region of the CD18 promoter that contains two binding sites for the PU.1 transcription factor is required for activity in myeloid cells. These sites are bound by in vitro translated PU.1 and by PU.1 from myeloid nuclear extracts. Mutagenesis of these sites abrogates binding by PU.1 and substantially decreases promoter activity in myeloid cells. Thus, the leukocyte-specific transcription factor PU.1 is required for myeloid activity of CD18.

Full text

PDF
805

Images in this article

802Fig. 1
on p.802
803Fig. 2
on p.803
803Fig. 3
on p.803
803Fig. 4
on p.803
804Fig. 5
on p.804

Selected References

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

  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. Brown T. A., McKnight S. L. Specificities of protein-protein and protein-DNA interaction of GABP alpha and two newly defined ets-related proteins. Genes Dev. 1992 Dec;6(12B):2502–2512. doi: 10.1101/gad.6.12b.2502. [DOI] [PubMed] [Google Scholar]
  3. Böttinger E. P., Shelley C. S., Farokhzad O. C., Arnaout M. A. The human beta 2 integrin CD18 promoter consists of two inverted Ets cis elements. Mol Cell Biol. 1994 Apr;14(4):2604–2615. doi: 10.1128/mcb.14.4.2604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen H. M., Pahl H. L., Scheibe R. J., Zhang D. E., Tenen D. G. The Sp1 transcription factor binds the CD11b promoter specifically in myeloid cells in vivo and is essential for myeloid-specific promoter activity. J Biol Chem. 1993 Apr 15;268(11):8230–8239. [PubMed] [Google Scholar]
  5. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Galson D. L., Housman D. E. Detection of two tissue-specific DNA-binding proteins with affinity for sites in the mouse beta-globin intervening sequence 2. Mol Cell Biol. 1988 Jan;8(1):381–392. doi: 10.1128/mcb.8.1.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Han J., Unlap T., Rado T. A. Expression of the human neutrophil elastase gene: positive and negative transcriptional elements in the 5' flanking region. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1462–1468. doi: 10.1016/0006-291x(91)92104-r. [DOI] [PubMed] [Google Scholar]
  9. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  13. Nordeen S. K. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988 May;6(5):454–458. [PubMed] [Google Scholar]
  14. Pahl H. L., Rosmarin A. G., Tenen D. G. Characterization of the myeloid-specific CD11b promoter. Blood. 1992 Feb 15;79(4):865–870. [PubMed] [Google Scholar]
  15. Pahl H. L., Scheibe R. J., Zhang D. E., Chen H. M., Galson D. L., Maki R. A., Tenen D. G. The proto-oncogene PU.1 regulates expression of the myeloid-specific CD11b promoter. J Biol Chem. 1993 Mar 5;268(7):5014–5020. [PubMed] [Google Scholar]
  16. Pongubala J. M., Nagulapalli S., Klemsz M. J., McKercher S. R., Maki R. A., Atchison M. L. PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity. Mol Cell Biol. 1992 Jan;12(1):368–378. doi: 10.1128/mcb.12.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pongubala J. M., Van Beveren C., Nagulapalli S., Klemsz M. J., McKercher S. R., Maki R. A., Atchison M. L. Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science. 1993 Mar 12;259(5101):1622–1625. doi: 10.1126/science.8456286. [DOI] [PubMed] [Google Scholar]
  18. Ray D., Bosselut R., Ghysdael J., Mattei M. G., Tavitian A., Moreau-Gachelin F. Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1. Mol Cell Biol. 1992 Oct;12(10):4297–4304. doi: 10.1128/mcb.12.10.4297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roberts W. M., Shapiro L. H., Ashmun R. A., Look A. T. Transcription of the human colony-stimulating factor-1 receptor gene is regulated by separate tissue-specific promoters. Blood. 1992 Feb 1;79(3):586–593. [PubMed] [Google Scholar]
  20. Rosmarin A. G., Levy R., Tenen D. G. Cloning and analysis of the CD18 promoter. Blood. 1992 May 15;79(10):2598–2604. [PubMed] [Google Scholar]
  21. Rosmarin A. G., Weil S. C., Rosner G. L., Griffin J. D., Arnaout M. A., Tenen D. G. Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation. Blood. 1989 Jan;73(1):131–136. [PubMed] [Google Scholar]
  22. Scott E. W., Simon M. C., Anastasi J., Singh H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science. 1994 Sep 9;265(5178):1573–1577. doi: 10.1126/science.8079170. [DOI] [PubMed] [Google Scholar]
  23. Todd R. F., 3rd, Freyer D. R. The CD11/CD18 leukocyte glycoprotein deficiency. Hematol Oncol Clin North Am. 1988 Mar;2(1):13–31. [PubMed] [Google Scholar]
  24. Voso M. T., Burn T. C., Wulf G., Lim B., Leone G., Tenen D. G. Inhibition of hematopoiesis by competitive binding of transcription factor PU.1. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7932–7936. doi: 10.1073/pnas.91.17.7932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zhang D. E., Hetherington C. J., Chen H. M., Tenen D. G. The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. Mol Cell Biol. 1994 Jan;14(1):373–381. doi: 10.1128/mcb.14.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES