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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-03-0680.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 894-902
HEMATOPOIESIS
The zinc finger transcription factor ZBP-89 is a repressor of
the human  2-integrin CD11b gene
Heiyoung Park,
C. Simon Shelley, and
M. Amin Arnaout
From the Leukocyte Biology and Inflammation Program,
Renal Unit, Massachusetts General Hospital, Harvard Medical School,
Boston, MA.
Integrin CD11b is a differentiation marker of the myelomonocytic
lineage and an important mediator of inflammation. Expression of the
CD11b gene is transcriptionally induced as myeloid
precursors differentiate into mature cells, then drops as monocytes
further differentiate into macrophages. Previous studies have
identified elements and factors involved in the transcriptional
activation of the CD11b gene during myeloid
differentiation, but no data exist regarding potential down-regulatory
factors, especially in the later stages of differentiation. Using 2 copies of a GC-rich element ( 141 to 110) in the CD11b
promoter, we probed a cDNA expression library for interacting proteins.
Three clones were identified among 9.1 million screened, all encoding
the DNA-binding domain of the zinc finger factor ZBP-89. Overexpression
of ZBP-89 in the monocyte precursor cell line U937 reduced
CD11b promoter-driven luciferase activity when U937 cells
were induced to differentiate into monocytelike cells using phorbol
esters. To identify the differentiation stage at which ZBP-89
repression of the CD11b gene is exerted, the protein level
of ZBP-89 was correlated with that of CD11b mRNA in differentiating
U937 as well as in normal human monocytes undergoing in vitro
differentiation into macrophages. A clear inverse relationship was
observed in the latter but not the former state, suggesting that ZBP-89
represses CD11b gene expression during the further
differentiation of monocytes into macrophages.
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