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Blood, 15 July 2002, Vol. 100, No. 2, pp. 483-490
HEMATOPOIESIS
Granulocyte inducer C/EBP inactivates the myeloid master
regulator PU.1: possible role in lineage commitment decisions
Venkateshwar A. Reddy,
Atsushi Iwama,
Guergana Iotzova,
Mathias Schulz,
Annika Elsasser,
Rajani K. Vangala,
Daniel G. Tenen,
Wolfgang Hiddemann, and
Gerhard Behre
From the Department of Medicine III,
Ludwig-Maximilians-University and GSF-National Research Center for
Environment and Health, Munich, Germany; Department of Immunology,
Institute of Basic Medical Sciences, University of Tsukuba Ibaraki,
Japan; and Harvard Institutes of Medicine, Harvard Medical School,
Boston, MA.
Several transcription factors have been implicated as playing a
role in myelopoiesis. PU.1, an ets-family transcription factor, is
required for the development of myeloid and lymphoid lineages, whereas
the transcription factor CCAAT-enhancer binding protein family member
C/EBP is essential for granulocyte development. We present here the
first evidence that C/EBP blocks the function of PU.1. PU.1 and
C/EBP interact physically and colocalize in myeloid cells. As a
consequence of this interaction, C/EBP can inhibit the function of
PU.1 to activate a minimal promoter containing only PU.1 DNA-binding
sites. We further demonstrate that the leucine zipper in the
DNA-binding domain of C/EBP interacts with the  3/4 region in
the DNA-binding domain of PU.1 and as a result displaces the PU.1
coactivator c-Jun. Finally, C/EBP blocks PU.1-induced dendritic cell
development from CD34+ human cord blood cells. The
functional blocking of PU.1 by C/EBP could be the mechanism by which
C/EBP inhibits cell fates specified by PU.1 and directs cell
development to the granulocyte lineage.
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