Chiba T, Ikawa Y, Todokoro K
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nucleic Acids Res. 1991 Jul 25;19(14):3843-8. doi: 10.1093/nar/19.14.3843.
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.
促红细胞生成素是一种细胞因子，它特异性地调节红系祖细胞的增殖和分化。促红细胞生成素受体在祖细胞膜上的表达是红系分化过程中的一个关键事件。为了阐明促红细胞生成素受体基因的组织特异性和分化阶段特异性表达，通过瞬时表达分析、凝胶迁移率变动分析和DNase I足迹分析对其转录调控进行了研究。结果清楚地表明，GATA-1通过位于起始密码子上游约-200 bp处的单个GATA基序以剂量依赖的方式反式激活基因表达。此外，Northern印迹分析显示，促红细胞生成素受体介导的信号随着血红蛋白阳性细胞的出现而强烈增强GATA-1基因表达。结合其他观察结果，这些结果提示了如下红系分化模式：1）GATA-1在血细胞发育的早期表达；2）GATA-1反式激活促红细胞生成素受体基因；3）促红细胞生成素与其受体结合，受体介导的信号增强红系祖细胞中GATA-1基因的表达；4）GATA-1最终在相对成熟的红细胞中反式激活血红蛋白合成相关基因和珠蛋白基因。
