GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression.
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.
Chiba
T
T
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Ikawa
Y
Y
Todokoro
K
K
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000378:metabolism*; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017467:Receptors, Erythropoietin; D015183:Restriction Mapping; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; D004921:Erythropoietin; D004247:DNA; D003850:Deoxyribonuclease I