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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smith, L. Articles by Tenen, D. Search for Related Content PubMed PubMed Citation Articles by Smith, L. Articles by Tenen, D. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony- stimulating factor receptor promoter in myeloid cells LT Smith, S Hohaus, DA Gonzalez, SE Dziennis and DG Tenen Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA. Cytokines, important for lineage commitment and differentiation during hematopoiesis, exert their influence by binding specific receptors. Receptor expression is tightly regulated and examining the factors that govern their expression will allow better understanding of the events that determine lineage commitment. The granulocyte colony-stimulating factor (G-CSF) receptor is expressed exclusively in myeloid cells and the placenta. We show here that the G-CSF receptor transcription start site is identical in each of these tissues. A 1,391-bp fragment of the G-CSF receptor promoter is both active in myeloid cell lines and tissue specific. We have also found two regions that are important for G-CSF receptor promoter activity. One region, located at bp -49, contains a GCAAT site that specifically binds the C/EBP alpha transcription factor in myeloid nuclear extracts. Mutation of this site prevents C/EBP alpha binding and reduces promoter activity by 60%. The other functionally important region of the G-CSF receptor promoter is in the 5' untranslated region, at bp +36 and +43, where there are two sites for the ets family member PU.1. Mutation of these sites prevents PU.1 binding and reduces promoter activity by 75%. These results reinforce the importance of both PU.1 and C/EBP alpha in the expression of myeloid-specific genes and neutrophil development. Volume 88, Issue 4, pp. 1234-1247, 08/15/1996 Copyright © 1996 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. M. Starnes, A. Sorrentino, E. Pelosi, M. Ballarino, O. Morsilli, M. Biffoni, S. Santoro, N. Felli, G. Castelli, M. L. De Marchis, et al. NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls {beta}-globin and G-CSF receptor expression Blood, August 27, 2009; 114(9): 1753 - 1763. 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Tenen A Transcriptional Profiling Study of CCAAT/Enhancer Binding Protein Targets Identifies Hepatocyte Nuclear Factor 3{beta} as a Novel Tumor Suppressor in Lung Cancer Cancer Res., June 15, 2004; 64(12): 4137 - 4147. [Abstract] [Full Text] [PDF] F. Rosenbauer, K. Wagner, P. Zhang, K.-P. Knobeloch, A. Iwama, and D. G. Tenen pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1 Blood, June 1, 2004; 103(11): 4294 - 4301. [Abstract] [Full Text] [PDF] C. K. Hwang, C. S. Kim, H. S. Choi, S. R. McKercher, and H. H. Loh Transcriptional Regulation of Mouse {micro} Opioid Receptor Gene by PU.1 J. Biol. Chem., May 7, 2004; 279(19): 19764 - 19774. [Abstract] [Full Text] [PDF] M. Schwieger, J. Lohler, M. Fischer, U. Herwig, D. G. Tenen, and C. 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Friedman C/EBPalpha Bypasses Granulocyte Colony-Stimulating Factor Signals to Rapidly Induce PU.1 Gene Expression, Stimulate Granulocytic Differentiation, and Limit Proliferation in 32D cl3 Myeloblasts Blood, July 15, 1999; 94(2): 560 - 571. [Abstract] [Full Text] [PDF] J. A. Lekstrom-Himes, S. E. Dorman, P. Kopar, S. M. Holland, and J. I. Gallin Neutrophil-specific Granule Deficiency Results from a Novel Mutation with Loss of Function of the Transcription Factor CCAAT/Enhancer Binding Protein {varepsilon} J. Exp. Med., June 7, 1999; 189(11): 1847 - 1852. [Abstract] [Full Text] [PDF] W. Verbeek, A. F. Gombart, A. M. Chumakov, C. Muller, A. D. Friedman, and H. P. Koeffler C/EBP{varepsilon} Directly Interacts With the DNA Binding Domain of c-myb and Cooperatively Activates Transcription of Myeloid Promoters Blood, May 15, 1999; 93(10): 3327 - 3337. [Abstract] [Full Text] [PDF] J. Lekstrom-Himes and K. G. Xanthopoulos CCAAT/Enhancer Binding Protein varepsilon  Is Critical for Effective Neutrophil-Mediated Response to Inflammatory Challenge Blood, May 1, 1999; 93(9): 3096 - 3105. [Abstract] [Full Text] [PDF] W.-F. Shen, S. Rozenfeld, A. Kwong, L. G. Komuves, H. J. Lawrence, and C. Largman HOXA9 Forms Triple Complexes with PBX2 and MEIS1 in Myeloid Cells Mol. Cell. Biol., April 1, 1999; 19(4): 3051 - 3061. [Abstract] [Full Text] [PDF] B. S. Egan, K. B. Lane, and V. L. Shepherd PU.1 and USF Are Required for Macrophage-specific Mannose Receptor Promoter Activity J. Biol. Chem., March 26, 1999; 274(13): 9098 - 9107. [Abstract] [Full Text] [PDF] G. Behre, A. J. Whitmarsh, M. P. Coghlan, T. Hoang, C. L. Carpenter, D.-E. Zhang, R. J. Davis, and D. G. Tenen c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor J. Biol. Chem., February 19, 1999; 274(8): 4939 - 4946. [Abstract] [Full Text] [PDF] M. Weiss, L. L. Moldawer, and E. M. Schneider Granulocyte Colony-Stimulating Factor to Prevent the Progression of Systemic Nonresponsiveness in Systemic Inflammatory Response Syndrome and Sepsis Blood, January 15, 1999; 93(2): 425 - 439. [Full Text] [PDF] N. C. Wilkinson and J. Navarro PU.1 Regulates the CXCR1 Promoter J. Biol. Chem., January 1, 1999; 274(1): 438 - 443. [Abstract] [Full Text] [PDF] T. B. van Dijk, B. Baltus, E. Caldenhoven, H. Handa, J. A.M. Raaijmakers, J.-W. J. Lammers, L. Koenderman, and R. P. de Groot Cloning and Characterization of the Human Interleukin-3 (IL-3)/IL-5/ Granulocyte-Macrophage Colony-Stimulating Factor Receptor beta c Gene: Regulation by Ets Family Members Blood, November 15, 1998; 92(10): 3636 - 3646. [Abstract] [Full Text] [PDF] J. Lekstrom-Himes and K. G. Xanthopoulos Biological Role of the CCAAT/Enhancer-binding Protein Family of Transcription Factors J. Biol. Chem., October 30, 1998; 273(44): 28545 - 28548. [Abstract] [Full Text] [PDF] P. Zhang, A. Iwama, M. W. Datta, G. J. Darlington, D. C. Link, and D. G. Tenen Upregulation of Interleukin 6 and Granulocyte Colony-Stimulating Factor Receptors by Transcription Factor CCAAT Enhancer Binding Protein {alpha} (C/EBP{alpha}) Is Critical for Granulopoiesis J. Exp. Med., September 21, 1998; 188(6): 1173 - 1184. [Abstract] [Full Text] [PDF] K. L. Anderson, K. A. Smith, F. Pio, B. E. Torbett, and R. A. Maki Neutrophils Deficient in PU.1 Do Not Terminally Differentiate or Become Functionally Competent Blood, September 1, 1998; 92(5): 1576 - 1585. [Abstract] [Full Text] [PDF] M. S. Petrovick, S. W. Hiebert, A. D. Friedman, C. J. Hetherington, D. G. Tenen, and D.-E. Zhang Multiple Functional Domains of AML1: PU.1 and C/EBPalpha Synergize with Different Regions of AML1 Mol. Cell. Biol., July 1, 1998; 18(7): 3915 - 3925. [Abstract] [Full Text] H. S. Radomska, C. S. Huettner, P. Zhang, T. Cheng, D. T. Scadden, and D. G. Tenen CCAAT/Enhancer Binding Protein alpha  Is a Regulatory Switch Sufficient for Induction of Granulocytic Development from Bipotential Myeloid Progenitors Mol. Cell. Biol., July 1, 1998; 18(7): 4301 - 4314. [Abstract] [Full Text] Y. Yamaguchi, S. J. Ackerman, N. Minegishi, M. Takiguchi, M. Yamamoto, and T. Suda Mechanisms of Transcription in Eosinophils: GATA-1, but not GATA-2, Transactivates the Promoter of the Eosinophil Granule Major Basic Protein Gene Blood, May 1, 1998; 91(9): 3447 - 3458. [Abstract] [Full Text] [PDF] Y. Ma, Q. Su, and P. Tempst Differentiation-stimulated Activity Binds an ETS-like, Essential Regulatory Element in the Human Promyelocytic defensin-1 Promoter J. Biol. Chem., April 10, 1998; 273(15): 8727 - 8740. [Abstract] [Full Text] [PDF] T. B. van Dijk, E. Caldenhoven, J. A.M. Raaijmakers, J.-W. J. Lammers, L. Koenderman, and R. P. de Groot The Role of Transcription Factor PU.I in the Activity of the Intronic Enhancer of the Eosinophil-Derived Neurotoxin (RNS2) Gene Blood, March 15, 1998; 91(6): 2126 - 2132. [Abstract] [Full Text] [PDF] H. Ying, J.-F. Chang, and J. R. Parnes PU.1/Spi-1 Is Essential for the B Cell-Specific Activity of the Mouse CD72 Promoter J. Immunol., March 1, 1998; 160(5): 2287 - 2296. [Abstract] [Full Text] [PDF] J. J. Westendorf, C. M. Yamamoto, N. Lenny, J. R. Downing, M. E. Selsted, and S. W. Hiebert The t(8;21) Fusion Product, AML-1-ETO, Associates with C/EBP-alpha , Inhibits C/EBP-alpha -Dependent Transcription, and Blocks Granulocytic Differentiation Mol. Cell. Biol., January 1, 1998; 18(1): 322 - 333. [Abstract] [Full Text] C. Zhang, P. Gadue, E. Scott, M. Atchison, and M. Poncz Activation of the Megakaryocyte-specific Gene Platelet Basic Protein (PBP) by the Ets Family Factor PU.1 J. Biol. Chem., October 17, 1997; 272(42): 26236 - 26246. [Abstract] [Full Text] [PDF] E. Sterneck, L. Tessarollo, and P. F. Johnson An essential role for C/EBPbeta in female reproduction Genes & Dev., September 1, 1997; 11(17): 2153 - 2162. [Abstract] [Full Text] [PDF] T. Bellon, D. Perrotti, and B. Calabretta Granulocytic Differentiation of Normal Hematopoietic Precursor Cells Induced by Transcription Factor PU.1 Correlates With Negative Regulation of the c-myb Promoter Blood, September 1, 1997; 90(5): 1828 - 1839. [Abstract] [Full Text] [PDF] D. G. Tenen, R. Hromas, J. D. Licht, and D.-E. Zhang Transcription Factors, Normal Myeloid Development, and Leukemia Blood, July 15, 1997; 90(2): 489 - 519. [Full Text] [PDF] R. Yamanaka, G.-D. Kim, H. S. Radomska, J. Lekstrom-Himes, L. T. Smith, P. Antonson, D. G. Tenen, and K. G. Xanthopoulos CCAAT/enhancer binding protein varepsilon  is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing PNAS, June 10, 1997; 94(12): 6462 - 6467. [Abstract] [Full Text] [PDF] D.-E. Zhang, P. Zhang, N.-d. Wang, C. J. Hetherington, G. J. Darlington, and D. G. Tenen Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha -deficient mice PNAS, January 21, 1997; 94(2): 569 - 574. [Abstract] [Full Text] [PDF] J.-G. Tang and H. P. Koeffler Structural and Functional Studies of CCAAT/Enhancer-binding Protein epsilon J. Biol. Chem., May 18, 2001; 276(21): 17739 - 17746. [Abstract] [Full Text] [PDF]

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