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Hematopoietic differentiation involves the commitment of multipotent progenitors to a given lineage, followed by the maturation of the committed cells. To study the transcriptional events controlling these processes, we have investigated the role of C/EBP proteins in lineage choice of multipotent hematopoietic progenitors (MEPs) transformed by the E26 virus. We found that forced expression of either the alpha or beta isoforms of C/EBP in MEPs induced eosinophil differentiation and that in addition, C/EBPbeta could induce myeloid differentiation. Conversely, dominant-negative versions of C/EBPbeta inhibited myeloid differentiation. C/EBP-induced eosinophil differentiation could be separated into two distinct events, lineage commitment and maturation. Thus, eosinophils induced by transactivation-deficient C/EBPbeta alleles were found to be blocked in their maturation, whereas those expressing wild-type C/EBP proteins were not. Likewise, a 1-day activation of a conditional C/EBPbeta allele in multipotent progenitors led to the formation of immature eosinophils, whereas sustained activation produced mature eosinophils. These results show that C/EBP can induce both myeloid and eosinophil lineage commitment and that transactivation independent and dependent C/EBP functions are required during eosinophil lineage commitment and maturation, respectively.

Original publication

DOI

10.1101/gad.12.15.2413

Type

Journal article

Journal

Genes Dev

Publication Date

01/08/1998

Volume

12

Pages

2413 - 2423

Keywords

Alleles, Amino Acid Sequence, Animals, CCAAT-Enhancer-Binding Proteins, Cell Differentiation, Chickens, DNA-Binding Proteins, Eosinophils, Gene Expression Regulation, Developmental, Hematopoiesis, Hematopoietic Stem Cells, Models, Biological, Molecular Sequence Data, Nuclear Proteins, Receptors, Estrogen, Recombinant Fusion Proteins, Transcriptional Activation, Transfection