The Role of FLI-1 Transcription Factor in Erythroid Differentiation

Abstract

The ELI-1 oncogene is a member of the ETS family of transcription factors and has been associated with both normal and abnormal hematopoietic cell growth and lineage specific differentiation. It has previously been shown that retroviral mediated transfer and expression of ELI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. This study demonstrates that ELI-1 can also act as an inhibitor of erythroid differentiation. Following the induction of erythroid differentiation, HEL cells, a human pluripotent cell line expressed reduced levels of ELI-1 mRNA. In contrast, when ELI-1 is overexpressed in these cells, the level of erythroid specific markers is reduced. Furthermore, the ability of ELI-1 overexpressing cells to respond to erythroid inducers such as Hemin and Ara-C is inhibited. ELI-1 expression in both K562 and HEL cells resulted in significant reduction of the level of the GATA -1 mRNA, an erythroid-associated transcription factor. Additionally, expression of a GATA-1 promoter driven reporter construct in K562 is inhibited when cotransfected with a construct expressing ELI-i. These results support the hypothesis that ELI-1 can act both positively and negatively in the regulation of hematopoietic cell differentiation, and suggests that inhibition of GATA-1 expression may contribute to ELI-1-mediated inhibition of erythroid differentiation.