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Distinct C/EBP functions are required for eosinophil lineage commitment and maturation

Item Type:Article
Title:Distinct C/EBP functions are required for eosinophil lineage commitment and maturation
Creators Name:Nerlov, C. and McNagny, K.M. and Doederlein, G. and Kowenz-Leutz, E. and Graf, T.
Abstract: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.
Keywords:Hematopoietic Differentiation, Leukemia Virus, Multipotent Progenitor, Transcription Factor, Animals, Chickens
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:12
Number:15
Page Range:2413-2423
Date:1 August 1998
Official Publication:https://doi.org/10.1101/gad.12.15.2413
PubMed:View item in PubMed

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