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Science 26 May 2000:
Vol. 288. no. 5470, pp. 1439 - 1441
DOI: 10.1126/science.288.5470.1439
Prev | Table of Contents

Reports

Regulation of B Lymphocyte and Macrophage Development by Graded Expression of PU.1

Rodney P. DeKoter, Harinder Singh *

The ets family transcription factor PU.1 is required for the development of multiple lineages of the immune system. Using retroviral transduction of PU.1 complementary DNA into mutant hematopoietic progenitors, we demonstrate that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages. A low concentration of PU.1 protein induces the B cell fate, whereas a high concentration promotes macrophage differentiation and blocks B cell development. Conversely, a transcriptionally weakened mutant protein preferentially induces B cell generation. Our results suggest that graded expression of a transcription factor can be used to specify distinct cell fates in the hematopoietic system.

Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 South Maryland Avenue, MC1028, Chicago, IL 60637, USA.
*   To whom correspondence should be addressed. E-mail: hsingh{at}midway.uchicago.edu

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J. Virol. 77, 1584-1588
   Abstract »    Full Text »    PDF »
Endocytic Internalization of Adenovirus, Nonspecific Phagocytosis, and Cytoskeletal Organization Are Coordinately Regulated in Alveolar Macrophages by GM-CSF and PU.1.
P.-Y. Berclaz, Z. Zsengeller, Y. Shibata, K. Otake, S. Strasbaugh, J. A. Whitsett, and B. C. Trapnell (2002)
J. Immunol. 169, 6332-6342
   Abstract »    Full Text »    PDF »
GM-CSF, via PU.1, regulates alveolar macrophage Fcgamma R-mediated phagocytosis and the IL-18/IFN-gamma -mediated molecular connection between innate and adaptive immunity in the lung.
P.-Y. Berclaz, Y. Shibata, J. A. Whitsett, and B. C. Trapnell (2002)
Blood 100, 4193-4200
   Abstract »    Full Text »    PDF »
Novel Combinatorial Interactions of GATA-1, PU.1, and C/EBPepsilon Isoforms Regulate Transcription of the Gene Encoding Eosinophil Granule Major Basic Protein.
J. Du, M. J. Stankiewicz, Y. Liu, Q. Xi, J. E. Schmitz, J. A. Lekstrom-Himes, and S. J. Ackerman (2002)
J. Biol. Chem. 277, 43481-43494
   Abstract »    Full Text »    PDF »
Granulocyte inducer C/EBPalpha inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions.
V. A. Reddy, A. Iwama, G. Iotzova, M. Schulz, A. Elsasser, R. K. Vangala, D. G. Tenen, W. Hiddemann, and G. Behre (2002)
Blood 100, 483-490
   Abstract »    Full Text »    PDF »
Multiple PU.1 sites cooperate in the regulation of p40phox transcription during granulocytic differentiation of myeloid cells.
S.-L. Li, A. J. Valente, M. Qiang, W. Schlegel, M. Gamez, and R. A. Clark (2002)
Blood 99, 4578-4587
   Abstract »    Full Text »    PDF »
Control of Myeloid-specific Integrin alpha Mbeta 2 (CD11b/CD18) Expression by Cytokines Is Regulated by Stat3-dependent Activation of PU.1.
A. D. Panopoulos, D. Bartos, L. Zhang, and S. S. Watowich (2002)
J. Biol. Chem. 277, 19001-19007
   Abstract »    Full Text »    PDF »
Differentiation plasticity of hematopoietic cells.
T. Graf (2002)
Blood 99, 3089-3101
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CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor.
Q.-f. Wang and A. D. Friedman (2002)
Blood 99, 2776-2785
   Abstract »    Full Text »    PDF »
Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease.
F. Jundt, K. Kley, I. Anagnostopoulos, K. Schulze Probsting, A. Greiner, S. Mathas, C. Scheidereit, T. Wirth, H. Stein, and B. Dorken (2002)
Blood 99, 3060-3062
   Abstract »    Full Text »    PDF »
HOX-A10 regulates hematopoietic lineage commitment: evidence for a monocyte-specific transcription factor.
T. Taghon, F. Stolz, M. De Smedt, M. Cnockaert, B. Verhasselt, J. Plum, and G. Leclercq (2002)
Blood 99, 1197-1204
   Abstract »    Full Text »    PDF »
Interaction between the Hematopoietic Ets Transcription Factor Spi-B and the Coactivator CREB-binding Protein Associated with Negative Cross-talk with c-Myb.
H. Yamamoto, F. Kihara-Negishi, T. Yamada, M. Suzuki, T. Nakano, and T. Oikawa (2002)
Cell Growth Differ. 13, 69-75
   Abstract »    Full Text »    PDF »
The Transcription Factor PU.1, Necessary for B-Cell Development Is Expressed in Lymphocyte Predominance, But Not Classical Hodgkin's Disease.
E. Torlakovic, A. Tierens, H. D. Dang, and J. Delabie (2001)
Am. J. Pathol. 159, 1807-1814
   Abstract »    Full Text »    PDF »
Differential requirement for the transcription factor PU.1 in the generation of natural killer cells versus B and T cells.
F. Colucci, S. I. Samson, R. P. DeKoter, O. Lantz, H. Singh, and J. P. Di Santo (2001)
Blood 97, 2625-2632
   Abstract »    Full Text »    PDF »


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