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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

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