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Publication : GATA factors are essential for transcription of the survival gene E4bp4 and the viability response of interleukin-3 in Ba/F3 hematopoietic cells.

First Author  Yu YL Year  2002
Journal  J Biol Chem Volume  277
Issue  30 Pages  27144-53
PubMed ID  12023274 Mgi Jnum  J:78040
Mgi Id  MGI:2183142 Doi  10.1074/jbc.M200924200
Citation  Yu YL, et al. (2002) GATA factors are essential for transcription of the survival gene E4bp4 and the viability response of interleukin-3 in Ba/F3 hematopoietic cells. J Biol Chem 277(30):27144-53
abstractText  E4bp4, a member of the basic region/leucine zipper transcription factor superfamily, is up-regulated by the interleukin-3 (IL-3) signaling pathway and plays an important role in the anti-apoptotic response of IL-3. In this study, we demonstrated that E4bp4 is regulated by IL-3 mainly at the transcriptional level. Promoter analysis revealed that a GATA motif downstream of a major transcription initiation site is essential for E4bp4 expression in the IL-3-dependent Ba/F3 cell line. Gel shift assays demonstrated that both GATA-1 and GATA-2 proteins bind to the E4bp4 GATA site in vitro, and the chromatin immunoprecipitation assay further confirmed the in vivo binding of GATA-1 to the E4bp4 promoter. Overexpression of GATA-1 alone transactivates the E4bp4 reporter, whereas transactivation of the E4bp4 reporter by GATA-2 is dependent on the stimulation of IL-3. Last, we demonstrated that alteration of GATA-1 binding to the GATA site by stably overexpressing GATA-1 or a GATA-1 mutant containing only the DNA-binding domain not only modulates the expression of the E4bp4 gene but also influences apoptosis induced by IL-3 removal. Taken together, our results suggest that the GATA factors play an important role in transducing the survival signal of IL-3, and one of their cellular targets is E4bp4.
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