FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells.

The FLI-1 oncogene, a member of the ETS family of transcription factors, is associated with both normal and abnormal hematopoietic cell growth and lineage-specific differentiation. We have previously shown that overexpression of FLI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. In this report we show that FLI-1 also acts as an inhibitor of erythroid differentiation.

Transactivation of the GATA-1 promoter by a myb-ets-containing mouse retrovirus is mediated by CACCC elements.

The myb-ets-containing ME26 virus causes erythroleukemia in mice by a novel mechanism involving the inappropriate activation of erythroid-specific genes in hematopoietic precursor cells. We have previously shown that the ME26 viral protein can transactivate the GATA-1 promoter in transient transactivation assays carried out in mouse fibroblasts. The mouse GATA-1 promoter, whose activity is regulated by the GATA-1 protein itself, contains a double GATA consensus sequence at its 5' end and two CACCC elements at its 3' end, both of which are crucial for promoter activity in erythroid cells, as well as a nonconsensus GATA sequence and several putative c-myb and c-ets binding sites.

MNU affects mouse erythroleukemia cell differentiation at sub-cytotoxic doses.

MNU is a potent carcinogen and mutagen to various tissues. Molecular events during differentiation show particular sensitivity to MNU exposure. We have investigated the mouse erythroleukemia (MEL) cell differentiation in response to DMSO and the influence of subcytotoxic doses of MNU on this process to assess the role of MNU on the course of differentiation and specific gene expression in a single cell type.

Nuclear proteins that interact with the beta maj globin promoter start to accumulate in MEL cells within 12 hours of induction and RNA copies of the promoter successfully compete their binding in vitro.

The induction of differentiation in mouse erythroleukemia (MEL) cells by dimethylsulfoxide (DMSO) is characterized by increased transcription of globin genes. We have determined that DMSO treated cells increase the levels of nuclear factors capable of overall interactions with the beta maj globin promoter during the initial 24 h post induction, as measured by gel mobility analysis. Two unprocessed beta maj globin mRNA precursors, which are present in MEL cell nuclei early in differentiation, were previously shown to contain the 5' promoter flanking region, and thereby provided the nucleus with a pool of regulatory sequences in multiple RNA copies.