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

The commitment of multipotent cells to particular developmental pathways re quires specific changes in their transcription factor complement to generat e 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 th at multipotent cells express high levels of FOG mRNA, which were rapidly do wn-regulated upon their C/EBP beta-mediated commitment to the eosinophil li neage. Expression of FOG in eosinophils led to a loss of eosinophil markers and the acquisition of a multipotent phenotype, and constitutive expressio n of FOG in multipotent progenitors blocked activation of eosinophil-specif ic gene expression by C/EBP beta. Our results show that FOG is a repressor of the eosinophil lineage, and that C/EBP-mediated down-regulation of FOG i s a critical step in eosinophil lineage commitment. Furthermore, our result s indicate that maintenance of a multipotent state in hematopoiesis is achi eved through cooperation between FOG and GATA-1. We present a model in whic h C/EBP beta induces eosinophil differentiation by the coordinate direct ac tivation of eosinophil-specific promoters and the removal of FOG, a promote r of multipotency as well as a repressor of eosinophil gene expression.