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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1448-1455.
Prepublished online as a Blood First Edition Paper on October 26, 2004; DOI 10.1182/blood-2003-11-4068.


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Submitted December 1, 2003
Accepted October 5, 2004

Gfi-1B plays a critical role in terminal differentiation of normal and transformed erythroid progenitor cells

Loic Garcon, Catherine Lacout, Fedor Svinartchouk, Jean-Pierre Le Couedic, Jean-Luc Villeval, William Vainchenker, and Dominique Dumenil*

INSERM U362, Institut Gustave Roussy, Villejuif, France

* Corresponding author; email: dumenil{at}cochin.inserm.fr.

Gfi-1B is a transcription factor with a highly conserved transcriptional repressor SNAG domain and six 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 progenitors cells. We studied the consequences of variations in Gfi-1B expression in two 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 CFU-E stage led to a partial GPA induction after 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.


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