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PMID: 11018018 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Antagonism between C/EBPbeta and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors.

Genes & development ·Vol. 14 ·No. 19 ·2000-10-01 ·Pages 2515-25

Querfurth E, Schuster M, Kulessa H, Crispino JD, Döderlein G, Orkin SH, Graf T, Nerlov C

Abstract

The commitment of multipotent cells to particular developmental pathways requires specific changes in their transcription factor complement to generate the patterns of gene expression characteristic of specialized cell types. We have studied the role of the GATA cofactor Friend of GATA (FOG) in the differentiation of avian multipotent hematopoietic progenitors. We found that multipotent cells express high levels of FOG mRNA, which were rapidly down-regulated upon their C/EBPbeta-mediated commitment to the eosinophil lineage. Expression of FOG in eosinophils led to a loss of eosinophil markers and the acquisition of a multipotent phenotype, and constitutive expression of FOG in multipotent progenitors blocked activation of eosinophil-specific gene expression by C/EBPbeta. Our results show that FOG is a repressor of the eosinophil lineage, and that C/EBP-mediated down-regulation of FOG is a critical step in eosinophil lineage commitment. Furthermore, our results indicate that maintenance of a multipotent state in hematopoiesis is achieved through cooperation between FOG and GATA-1. We present a model in which C/EBPbeta induces eosinophil differentiation by the coordinate direct activation of eosinophil-specific promoters and the removal of FOG, a promoter of multipotency as well as a repressor of eosinophil gene expression.

MeSH Terms
Animals Avian Proteins CCAAT-Enhancer-Binding Protein-beta/metabolism Carrier Proteins/metabolism Cell Differentiation Cell Lineage Chick Embryo DNA-Binding Proteins Down-Regulation Eosinophils/cytology,metabolism Erythroid-Specific DNA-Binding Factors Gene Expression Regulation Hematopoietic Stem Cells/cytology,metabolism Membrane Glycoproteins/genetics Models, Genetic Myeloid Cells Nuclear Proteins/metabolism Phenotype Promoter Regions, Genetic Transcription Factors
Chemicals
Avian Proteins CCAAT-Enhancer-Binding Protein-beta Carrier Proteins DNA-Binding Proteins EOS47 protein, Gallus gallus Erythroid-Specific DNA-Binding Factors Membrane Glycoproteins Nuclear Proteins Transcription Factors ZFPM1 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Querfurth E
Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
Schuster M
Kulessa H
Crispino J D
Döderlein G
Orkin S H
Graf T
Nerlov C
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.177200
Published
2000-10-01
Pages
2515-25
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316981
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.177200 PMC Full Text View journal details
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