Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential 
for erythropoiesis and megakaryopoiesis. Targeted gene disruption of GFI1B in 
mice leads to embryonic lethality resulting from failure to produce definitive 
erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis. We 
here show that, in humans, Gfi-1B controls the development of erythrocytes and 
megakaryocytes by regulating the proliferation and differentiation of bipotent 
erythro-megakaryocytic progenitors. We further identify in this cell population 
the type III transforming growth factor-beta receptor gene, TGFBR3, as a direct 
target of Gfi-1B. Knockdown of Gfi-1B results in altered transforming growth 
factor-beta (TGF-beta) signaling as shown by the increase in Smad2 
phosphorylation and its inability to associate to the transcription intermediary 
factor 1-gamma (TIF1-gamma). Because the Smad2/TIF1-gamma complex is known to 
specifically regulate erythroid differentiation, we propose that, by repressing 
TGF-beta type III receptor (TbetaRIotaII) expression, Gfi-1B favors the 
Smad2/TIF1-gamma interaction downstream of TGF-beta signaling, allowing immature 
progenitors to differentiate toward the erythroid lineage.