Zon L I, Youssoufian H, Mather C, Lodish H F, Orkin S H
Division of Hematology-Oncology, Children's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10638-41. doi: 10.1073/pnas.88.23.10638.
Erythropoietin, a glycoprotein produced by the kidneys in response to anemia and hypoxia, is a major growth factor for cells of the erythroid lineage. Erythropoietin interacts with high-affinity cell surface receptors (EpoR) present on developing progenitors and is required for their survival. Previously we characterized the gene for EpoR and demonstrated that its promoter acts in a cell-specific manner. Here we show that the hematopoietic-specific transcription factor GATA-1 is necessary, and indeed is sufficient as the sole cell-restricted regulator, for activation of the EpoR promoter in fibroblast transfection assays. Hence, GATA-1, which participates in transcriptional control of the majority of erythroid-expressed genes, also acts on the promoter of an essential lineage-restricted receptor (EpoR). This central contribution of GATA-1 to EpoR promoter function provides a mechanism whereby a cell-restricted regulator may ensure the viability and subsequent maturation of progenitor cells during hematopoietic differentiation.
促红细胞生成素是一种由肾脏在贫血和缺氧状态下产生的糖蛋白，是红系谱系细胞的主要生长因子。促红细胞生成素与发育中的祖细胞上存在的高亲和力细胞表面受体（EpoR）相互作用，是这些祖细胞存活所必需的。我们之前对EpoR基因进行了表征，并证明其启动子以细胞特异性方式发挥作用。在此我们表明，在成纤维细胞转染实验中，造血特异性转录因子GATA-1对于激活EpoR启动子是必需的，而且作为唯一的细胞限制性调节因子实际上也是足够的。因此，参与大多数红系表达基因转录调控的GATA-1，也作用于一种必需的谱系限制性受体（EpoR）的启动子。GATA-1对EpoR启动子功能的这一核心贡献提供了一种机制，通过该机制，一种细胞限制性调节因子可确保造血分化过程中祖细胞的存活及随后的成熟。
