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Molecular and Cellular Biology, February 2003, p. 1390-1402, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1390-1402.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Functional Cross-Antagonism between Transcription Factors FLI-1 and EKLF

Joëlle Starck,1 Nathalie Cohet,1 Colette Gonnet,1 Sandrine Sarrazin,1,{dagger} Zina Doubeikovskaia,2 Alexandre Doubeikovski,3 Alexis Verger,4 Martine Duterque-Coquillaud,4 and François Morle1*

Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, 69622 Villeurbanne,1 Institut de Biologie de Lille, CNRS UMR 8526, 59021 Lille cedex, France,4 Institute of Biochemistry and Physiology of Microorganisms, Moscow 142292, Russia,2 Weis Center for Research, Danville, Pennsylvania 17822-26143

Received 18 July 2002/ Returned for modification 18 September 2002/ Accepted 18 November 2002

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 ß-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 ß-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.

* Corresponding author. Mailing address: Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France. Phone: (33) 04 72 43 13 75. Fax: (33) 04 72 44 05 55. E-mail: morle{at}cismsun.univ-lyon1.fr.

{dagger} Present address: CIML, 13288 Marseille, France.

Molecular and Cellular Biology, February 2003, p. 1390-1402, Vol. 23, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.4.1390-1402.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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