Gfi-1B plays a critical role in terminal differentiation of normal and transformed erythroid progenitor cells.
Growth factor independence-1B (Gfi-1B) is a transcription factor with a highly conserved transcriptional repressor snail-Gfi-1 (SNAG) domain and 6 zinc-finger domains at the N- and C-terminus, respectively. Disruption of the Gfi-1B gene is lethal in the embryo with failure to produce definitive enucleated erythrocytes. In this study, we analyzed the role of Gfi-1B in human erythropoiesis. We observed an increase of Gfi-1B expression during erythroid maturation of human primary progenitor cells. We studied the consequences of variations in Gfi-1B expression in 2 transformed cell lines (K562 and UT7 cells), as well as in primary CD36(+)/GPA(-) progenitors. A knock-down of Gfi-1B delayed the terminal differentiation of K562 and primary cells. Forced expression of Gfi-1B in UT7 and K562 cells led to an arrest of proliferation and an induction of erythroid differentiation. Enforced expression of Gfi-1B in primary cells at the colony-forming units-erythroid (CFU-E) stage led to a partial glycophorin A (GPA) induction after erythropoietin (EPO) withdrawal but failed to protect cells from apoptosis. Deletion of the SNAG repressor domain abolished Gfi-1B-induced erythroid maturation, strongly suggesting that Gfi-1B acts in the late stage of erythroid differentiation as a transcriptional repressor.
Garçon
Loïc
L
Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Institut Gustave Roussy, 94805 Villejuif cedex, France.
Lacout
Catherine
C
Svinartchouk
Fédor
F
Le Couédic
Jean-Pierre
JP
Villeval
Jean-Luc
JL
Vainchenker
William
W
Duménil
Dominique
D
D018955:CD36 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000378:metabolism* / Q000473:pathology*; D004921:Erythropoietin / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
D018955:CD36 Antigens; C111977:GFI1B protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D004921:Erythropoietin