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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer binding proteins alpha and epsilon (C/ EBP alpha and C/ EBP epsilon ) and CDP/cut in myeloid maturation-induced lactoferrin gene expression.

In vitro models of granulopoiesis involving the inducible expression of either CCAAT enhancer binding protein alpha (C/ EBP alpha) or C/ EBP epsilon 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 alpha binds to the LF promoter in nonexpressing cells. Upon induction of maturation, C/ EBP epsilon 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 alpha, C/ EBP epsilon, and CDP/cut all play definitive roles in regulating late gene expression during normal myeloid development.[1]

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