Abstract
THE zinc-finger transcription factor GATA-1 (previously known as GF-1, NF-E1 or Eryf 1 (refs 1-5)) binds to GATA consensus elements in regulatory regions of theα- and β-globin gene clusters2–6 and other erythroid cell-specific genes7–9. Analysis of the effects of mutations in GATA-binding sites in cell culture and in binding assays in vitro2,5,10,11, as well as transactivation studies with GATA-1 expression vectors in heterologous cells12, have provided indirect evidence that this factor is involved in the activation of globin and other genes during erythroid cell maturation. GATA-1 is also expressed in megakaryocytes13,14 and mast cells13, but not in other blood cell lineages or in non-haemopoietic cells. To investigate the role of this factor in haematopoiesis in vivo. we disrupted the X-linked GATA-1 gene by homologous recombination in a male (XY) murine embryonic stem cell line and tested the GATA-1-deficient cells for their ability to contribute to different tissues in chimaeric mice. The mutant embryonic stem cells contributed to all non-haemopoietic tissues tested and to a white blood cell fraction, but failed to give rise to mature red blood cells. This demonstrates that GATA-1 is required for the normal differentiation of erythroid cells, and that other GATA-binding proteins15,16 cannot compensate for its absence.
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Pevny, L., Simon, M., Robertson, E. et al. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349, 257–260 (1991). https://doi.org/10.1038/349257a0
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DOI: https://doi.org/10.1038/349257a0
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