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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-09-2767.

Submitted September 10, 2002
Accepted December 18, 2002
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*
Department of Internal Medicine/Hematology, Yale University, New Haven, CT, USA
* Corresponding author; email: nancy.berliner{at}yale.edu.
In vitro models of granulopoiesis involving the inducible expression of either 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 ChIP analysis we demonstrate that C/EBP binds to the LF promoter in non-expressing 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 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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