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• W2164333337 abstract "AbstractThe transcription factor C/EBPα is crucial for the differentiation of granulocytes. Conditional expression of C/EBPα triggers neutrophilic differentiation, and C/EBPα can block 12-O-tetradecanoylphorbol-13-acetate-induced monocytic differentiation of bipotential myeloid cells. In C/EBPα knockout mice, no mature granulocytes are present. A dramatic increase of c-Jun mRNA in C/EBPα knockout mouse fetal liver was observed. c-Jun, a component of the AP-1 transcription factor complex and a coactivator of the transcription factor PU.1, is important for monocytic differentiation. Here we report that C/EBPα downregulates c-Jun expression to drive granulocytic differentiation. An ectopic increase of C/EBPα expression decreases the c-Jun mRNA level, and the human c-Jun promoter activity is downregulated eightfold in the presence of C/EBPα. C/EBPα and c-Jun interact through their leucine zipper domains, and this interaction prevents c-Jun from binding to DNA. This results in downregulation of c-Jun's capacity to autoregulate its own promoter through the proximal AP-1 site. Overexpression of c-Jun prevents C/EBPα-induced granulocytic differentiation. Thus, we propose a model in which C/EBPα needs to downregulate c-Jun expression and transactivation capacity for promoting granulocytic differentiation. We thank Hanna Radomska for valuable discussions and Diana Dudziak, Falk Nimmerjahn, Joachim Ellwart, Karin Nispel, and Susan King for technical support. Thanks also go to Torsten Haferlach for providing the differentials and imaging of the cytospins.This work was supported by DFG (German Research Foundation) grant 2042/2-1 to G.B." @default.
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• W2164333337 date "2002-12-01" @default.
• W2164333337 modified "2023-10-10" @default.
• W2164333337 title "Downregulation of c-Jun Expression by Transcription Factor C/EBPα Is Critical for Granulocytic Lineage Commitment" @default.
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• W2164333337 doi "https://doi.org/10.1128/mcb.22.24.8681-8694.2002" @default.
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