Nucleic Acids Research, 1991, Vol. 19, No. 14 3843-3848
© 1991
MOLECULAR BIOLOGY |
GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression
1Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN) 3-1, Kohyadai, Tsukuba, Ibaraki 305, Japan 2Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba 2-1, Tennoudai, Tsukuba, Ibaraki 305, Japan
* To whom correspondence should be addressed
Received May 16, 1991. Revised June 21, 1991. Accepted June 21, 1991.
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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