Regulation of Expression of the Human Erythropoietin Receptor Gene

ABSTRACT: Interactions between erythropoietin (Epo) and its receptor (EpoR) are critical for the normal proliferation and differentiation of erythroid progenitor cells. EpoR is expressed in low numbers during early stages of erythroid maturation, while higher levels are expressed during later stages, suggesting that the expression of the EpoR gene is tightly regulated throughout erythropoiesis. We used the TF-1 erythroleukemia cell line to analyze the effects of various cytokines and reagents on the regulation of human EpoR gene expression. Human EpoR gene expression was significantly upregulated by IL-1α and the protein inhibitor cycloheximide, but significantly downregulated by the calcium ionophore ionomycin and the phorbol ester PMA. These effects on EpoR gene expression were not due to changes in EpoR mRNA stability, suggesting that these agents directly affected EpoR gene transcription. The selectivein vitromodification of EpoR expression by these agents highlights the complexity of human EpoR gene expression, and provides clues to itsin vivoregulation.