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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-09-2767.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3460-3468
HEMATOPOIESIS
Chromatin immunoprecipitation (ChIP) studies indicate a
role for CCAAT enhancer binding proteins alpha and epsilon (C/EBP
and C/EBP ) and CDP/cut in myeloid maturation-induced lactoferrin
gene expression
Arati Khanna-Gupta,
Theresa Zibello,
Hong Sun,
Peter Gaines, and
Nancy Berliner
From the Section of Hematology, Department of Internal
Medicine, Yale University School of Medicine, New Haven, CT.
In vitro models of granulopoiesis involving the inducible
expression of either CCAAT enhancer binding protein alpha
(C/EBP ) or C/EBP in myeloid cells have been shown to lead
to the induction of a granulocytic maturation program accompanied by
the expression of myeloid-specific genes. Since members of the C/EBP
family of transcription factors recognize and bind to similar
DNA-binding motifs, it has been difficult to elucidate the specific
role of each of the C/EBP family members in eliciting myeloid gene
expression. In order to address this issue, we focused on the
expression of the lactoferrin (LF) gene. LF expression is
transcriptionally regulated in a C/EBP-dependent manner in myeloid
cells. Using chromatin immunoprecipitation (ChIP) analysis we
demonstrate that C/EBP binds to the LF promoter in
nonexpressing cells. Upon induction of maturation, C/EBP binds to
the LF promoter, which correlates with LF expression. Lack of LF
expression in the acute promyelocytic leukemia cell line NB4, which
harbors the t(15;17) translocation, cannot be correlated with aberrant
binding at the C/EBP site in the LF promoter. It is, however,
associated with the persistent binding of the silencer CCAAT
displacement protein (CDP/cut) to the LF promoter in these cells. We
conclude that C/EBP , C/EBP , and CDP/cut all play
definitive roles in regulating late gene expression during normal
myeloid development.

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