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  • The EMBO Journal (2008) 27, 2006 - 2017
  • doi:10.1038/emboj.2008.117

Published online: 19 June 2008

Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization

Ekaterina P Lamber1, Laurent Vanhille2,3,4, Larissa C Textor1, Galina S Kachalova5, Michael H Sieweke2,3,4 and Matthias Wilmanns1

  1. EMBL-Hamburg, c/o DESY, Hamburg, Germany
  2. Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France
  3. Institut National de la Santé et de la Recherche Médicale, Marseille, France
  4. Centre National de la Recherche Scientifique, Parc scientifique de Luminy, Marseille, France
  5. Max-Planck Unit for Structural Molecular Biology, c/o DESY, Hamburg, Germany

Correspondence to:

Matthias Wilmanns, EMBL Hamburg Outstation, EMBL c/o DESY, Notkestrasse 85, Building 25A, Hamburg D-22603, Germany. Tel.: +49 40 899 021 26; Fax: +49 40 899 021 49; E-mail: wilmanns@embl-hamburg.de

Received 15 November 2007; Accepted 23 May 2008

The function of the Ets-1 transcription factor is regulated by two regions that flank its DNA-binding domain. A previously established mechanism for auto-inhibition of monomeric Ets-1 on DNA response elements with a single ETS-binding site, however, has not been observed for the stromelysin-1 promoter containing two palindromic ETS-binding sites. We present the structure of Ets-1 on this promoter element, revealing a ternary complex in which protein homo-dimerization is mediated by the specific arrangement of the two ETS-binding sites. In this complex, the N-terminal-flanking region is required for ternary protein–DNA assembly. Ets-1 variants, in which residues from this region are mutated, loose the ability for DNA-mediated dimerization and stromelysin-1 promoter transactivation. Thus, our data unravel the molecular basis for relief of auto-inhibition and the ability of Ets-1 to function as a facultative dimeric transcription factor on this site. Our findings may also explain previous data of Ets-1 function in the context of heterologous transcription factors, thus providing a molecular model that could also be valid for Ets-1 regulation by hetero-oligomeric assembly.

  • Keywords:

    • Ets-1,
    • stromelysin-1 promoter,
    • X-ray crystallography