In the search for genes expressed in hematopoietic stem cells, we identified 
that the expression of Gfi-1B (growth factor independence-1B) is highly 
restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes. Gfi-1 
and Gfi-1B are zinc finger proteins that share highly conserved SNAG and 6 zinc 
finger domains. Gfi-1 has been characterized as an oncogene involved in lymphoid 
malignancies in mice. In contrast, role of Gfi-1B in hematopoiesis has not been 
well characterized. In this study, we analyzed its function in human 
hematopoiesis. Enforced expression of Gfi-1B in human CD34(+) hematopoietic 
progenitors induced a drastic expansion of erythroblasts in an 
erythropoietin-independent manner. Expression of Gfi-1B did not promote 
erythroid commitment, but enhanced proliferation of immature erythroblasts. 
Erythroblasts expanded by exogenous Gfi-1B, however, failed to differentiate 
beyond proerythroblast stage and showed massive apoptosis. These biologic 
effects of Gfi-1B were mediated through its zinc finger domain, but not by the 
SNAG or non-zinc finger domain. Proliferation of erythroblasts was associated 
with sustained expression of GATA-2 but not of GATA-1, indicating a potential 
link between Gfi-1B and GATA family regulators. Importantly, the function of 
Gfi-1B to modulate transcription was dependent on promoter context. In addition, 
activation of transcription of an artificial promoter was mediated through its 
zinc finger domain. These findings establish Gfi-1B as a novel erythroid 
regulator and reveal its specific involvement in the regulation of erythroid 
cell growth through modulating erythroid-specific gene expression.