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Mol. Cell. Biol. doi:10.1128/MCB.02212-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

GATA-1 and Gfi-1B Interplay to Regulate Bcl-x_L Transcription

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan, R.O.C.

^* To whom correspondence should be addressed. Email: ZFCHANG{at}ha.mc.ntu.edu.tw.

	Abstract

Induction of Bcl-x_L is critical for the survival of late proerythroblasts. The erythroid-specific transcriptional network that regulates Bcl-x_L expression in erythropoiesis remains unclear. Activation of the central erythropoietic transcriptional factor, GATA-1, leads to an early transient induction of a transcription repressor Gfi-1B followed by a late induction of Bcl-x_L during erythroid maturation in G1ER cells. ChIP assays demonstrated that GATA-1 binds to the Bcl-x promoter constantly in the entire induction period, while Gfi-1B is transiently associated with the promoter in the early phase. Sustained expression of Gfi-1B abolished GATA-1-induced Bcl-x_L expression. Here, we present evidence that GATA-1 binds to the non-canonical GATT motif of the Bcl-x promoter for trans-activation. Increased expression of Gfi-1B is recruited to the Bcl-x promoter through its association with GATA-1, suppressing Bcl-x_L transcription. Therefore, down-regulation of Gfi-1B in the late phase of erythroid maturation is necessary for Bcl-x_L induction. Furthermore, we show that inhibition of Bcr-Abl kinase by the imatinib treatment causes up-regulation of Gfi-1B in K562 cells, where it also cooperates with GATA-1 to repress Bcl-x_L transcription. Gfi-1B knockdown by RNA interference diminished imatinib-induced apoptosis, while overexpression of Gfi-1B sensitized K562 cells to arsenic-induced death. These findings illuminate the role of Gfi-1B in GATA-1-mediated transcription in the survival aspect of erythroid cells.