Functional cross-antagonism between transcription factors FLI-1 and EKLF.
FLI-1 is an ETS family transcription factor which is overexpressed in Friend erythroleukemia and contributes to the blockage of differentiation of erythroleukemic cells. We show here that FLI-1 represses the transcriptional activity of the beta-globin gene promoter in MEL cells and interacts with two of its critical transactivators, GATA-1 and ... EKLF. Unexpectedly, FLI-1 enhances the stimulating activity of GATA-1 on a GATA-1-responsive promoter but represses that of EKLF on beta-globin and an EKLF-responsive artificial promoters. This repressive effect of FLI-1 requires the ETS DNA binding domain and its association with either the N- or C-terminal domain, which themselves interact with EKLF but not with GATA-1. Furthermore, the FLI-1 ETS domain alone behaves as an autonomous repression domain when linked to the Gal4 DNA binding domain. Taken together, these data indicate that FLI-1 represses EKLF-dependent transcription due to the repression activity of its ETS domain and its indirect recruitment to erythroid promoters by protein-protein interaction with EKLF. Reciprocally, we also show that EKLF itself represses the FLI-1-dependent megakaryocytic GPIX gene promoter, thus further suggesting that functional cross-antagonism between FLI-1 and EKLF might be involved in the control of the erythrocytic versus megakaryocytic differentiation of bipotential progenitors.
Mesh Terms:
Acetamides, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, DNA, DNA-Binding Proteins, Erythrocytes, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Globins, Kruppel-Like Transcription Factors, Mice, Molecular Sequence Data, Platelet Glycoprotein GPIb-IX Complex, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Recombinant Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic
Acetamides, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, DNA, DNA-Binding Proteins, Erythrocytes, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Globins, Kruppel-Like Transcription Factors, Mice, Molecular Sequence Data, Platelet Glycoprotein GPIb-IX Complex, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Recombinant Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic
Mol. Cell. Biol.
Date: Feb. 01, 2003
PubMed ID: 12556498
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