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      GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression.

      Nucleic Acids Research
      Animals, Base Sequence, Cloning, Molecular, DNA, DNA-Binding Proteins, genetics, metabolism, Deoxyribonuclease I, Erythroid-Specific DNA-Binding Factors, Erythropoietin, GATA1 Transcription Factor, Gene Expression Regulation, Hematopoiesis, Leukemia, Erythroblastic, Acute, Mice, Molecular Sequence Data, Promoter Regions, Genetic, Receptors, Cell Surface, Receptors, Erythropoietin, Restriction Mapping, Signal Transduction, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured

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          Abstract

          Erythropoietin is a cytokine which specifically regulates the proliferation and differentiation of erythroid progenitor cells. The expression of erythropoietin receptor on the cell membrane of the progenitor cells is a critical event during the erythroid differentiation process. In order to clarify the tissue-specific and differentiation stage-specific expression of the erythropoietin receptor gene, its transcriptional regulation was examined by transient expression assay, gel mobility shift assay and DNase I footprinting. The results clearly showed that GATA-1 transactivates the gene expression through a single GATA motif located around -200 bp upstream from the ATG codon in a dose dependent manner. Furthermore, Northern blot analysis revealed that erythropoietin receptor-mediated signals strongly enhanced GATA-1 gene expression in accordance with the appearance of hemoglobin-positive cells. Taken together with other observations, these results suggested the following scheme of erythroid differentiation: 1)GATA-1 is expressed in the early stage of blood cell development; 2) GATA-1 transactivates the erythropoietin receptor gene; 3) erythropoietin binds its receptor and the receptor-mediated signals enhance GATA-1 gene expression in erythroid progenitor cells; and 4) GATA-1 finally transactivates hemoglobin synthesis-related genes and globin genes in relatively matured erythroid cells.

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