In contrast to the definitive role of the transcription factor, CCAAT/Enhancer 
binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings 
have suggested that granulopoiesis during emergency situations, such as 
infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based 
reporter system was developed to elucidate the molecular switch required for 
C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive 
elements (CREs) in the proximal promoter region of C/EBPβ were involved in the 
positive regulation of C/EBPβ transcription during granulocyte-macrophage 
colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. 
In addition, the transcripts of CRE binding (CREB) family proteins were readily 
detected in hematopoietic stem/progenitor cells. CREB was upregulated, 
phosphorylated and bound to the CREs in response to GM-CSF stimulation. 
Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA 
levels and significantly impaired the proliferation/differentiation of 
granulocyte precursors, while a constitutively active form of CREB facilitated 
C/EBPβ transcription. These data suggest that CREB proteins are involved in the 
regulation of granulopoiesis via C/EBPβ upregulation.