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Science 288 (5470): 1439-1441

Copyright © 2000 by the American Association for the Advancement of Science

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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   Abstract »    Full Text »    PDF »
Mast Cells Acquire Monocyte-Specific Gene Expression and Monocyte-Like Morphology by Overproduction of PU.1.
T. Ito, C. Nishiyama, M. Nishiyama, H. Matsuda, K. Maeda, Y. Akizawa, R. Tsuboi, K. Okumura, and H. Ogawa (2005)
J. Immunol. 174, 376-383
   Abstract »    Full Text »    PDF »
The ETS Transcription Factor Spi-B Is Required for Human Plasmacytoid Dendritic Cell Development.
R. Schotte, M. Nagasawa, K. Weijer, H. Spits, and B. Blom (2004)
J. Exp. Med. 200, 1503-1509
   Abstract »    Full Text »    PDF »
PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain.
W. D. Cook, B. J. McCaw, C. Herring, D. L. John, S. J. Foote, S. L. Nutt, and J. M. Adams (2004)
Blood 104, 3437-3444
   Abstract »    Full Text »    PDF »
Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible.
H. Tagoh, A. Schebesta, P. Lefevre, N. Wilson, D. Hume, M. Busslinger, and C. Bonifer (2004)
EMBO J. 23, 4275-4285
   Abstract »    Full Text »    PDF »
Form follows function: the genomic organization of cellular differentiation.
S. T. Kosak and M. Groudine (2004)
Genes & Dev. 18, 1371-1384
   Abstract »    Full Text »    PDF »
The roles of transcription factors in B lymphocyte commitment, development, and transformation.
E. Smith and M. Sigvardsson (2004)
J. Leukoc. Biol. 75, 973-981
   Abstract »    Full Text »    PDF »
The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15Ink4b in murine myeloid cells.
M. Schmidt, J. Bies, T. Tamura, K. Ozato, and L. Wolff (2004)
Blood 103, 4142-4149
   Abstract »    Full Text »    PDF »
pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1.
F. Rosenbauer, K. Wagner, P. Zhang, K.-P. Knobeloch, A. Iwama, and D. G. Tenen (2004)
Blood 103, 4294-4301
   Abstract »    Full Text »    PDF »
PU.1 determines the self-renewal capacity of erythroid progenitor cells.
J. Back, A. Dierich, C. Bronn, P. Kastner, and S. Chan (2004)
Blood 103, 3615-3623
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of the Cyclooxygenase-2 Gene in Macrophages by PU.1.
M. Joo, G. Y. Park, J. G. Wright, T. S. Blackwell, M. L. Atchison, and J. W. Christman (2004)
J. Biol. Chem. 279, 6658-6665
   Abstract »    Full Text »    PDF »

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