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

Erich Querfurth, Mikkel Schuster, Holger Kulessa, John D. Crispino, Gabriele Döderlein, Stuart H. Orkin, Thomas Graf, Claus Nerlov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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/EBPβ-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/EBPβ. 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/EBPβ 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.

Original languageEnglish (US)
Pages (from-to)2515-2525
Number of pages11
JournalGenes and Development
Volume14
Issue number19
DOIs
StatePublished - Oct 1 2000

Keywords

  • C/EBP
  • Eosinophil
  • FOG
  • GATA
  • Lineage commitment
  • Multipotent progenitor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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