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GATA-1 and c-myb crosstalk during red blood cell differentiation through GATA-1 binding sites in the c-myb promoter

Oncogene volume 22, pages 1927–1935 (2003)Cite this article

Abstract

GATA-1 and c-Myb transcription factors represent key regulators of red blood cell development. GATA-1 is upregulated and c-myb proto-oncogene expression is downregulated when red cell progenitors differentiate into erythrocytes. Here we have employed a culture system, that faithfully recapitulates red blood cell differentiation in vitro, to follow the kinetics of GATA-1 and c-myb expression. We show that c-myb proto-oncogene expression is high in progenitors and effectively downregulated at the time when nuclear GATA-1 accumulates and cells differentiate into erythrocytes. Additionally, we identified two GATA-1 binding sites within the c-myb promoter and demonstrate that GATA-1 protein binds to these sites in vitro. Furthermore, GATA-1 represses c-myb expression through one of the GATA-1 binding sites in transient transfection experiments and this requires FOG-1. Thus, our study provides evidence for a direct molecular link between GATA-1 activity and c-myb proto-oncogene expression during terminal red cell differentiation.

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Acknowledgements

We thank SH Orkin and H Wolfes for FOG-1 cDNA and expression plasmid, H Stunnenberg for His-huTBP, JD Engel for GST-GATA-1 and pLucβTATA, RH Nicolas for GATA-1 specific antibody and P Podlatis for expert secretarial assistance. Part of this work was funded by grants of the Grant Agency of the Czech Republic (301/98/K042) to MD, the Fonds der Chemischen Industrie to MZ and Volkswagen Foundation to PB and MZ.

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  1. Max-Delbrück-Center for Molecular Medicine, Robert-Rössle Str. 10, Berlin, D-13092, Germany

    Petr Bartůněk, Gitta Blendinger & Martin Zenke

  2. Institute of Molecular Genetics, Flemingovo nam. 2, Prague, 6, 16637, Czech Republic

    Petr Bartůněk, Jarmila Králová & Michal Dvořák

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  1. Petr Bartůněk
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Correspondence to Martin Zenke.

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Bartůněk, P., Králová, J., Blendinger, G. et al. GATA-1 and c-myb crosstalk during red blood cell differentiation through GATA-1 binding sites in the c-myb promoter. Oncogene 22, 1927–1935 (2003). https://doi.org/10.1038/sj.onc.1206281

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