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Regulation of the transcription factor Ets‐1 by DNA‐mediated homo‐dimerization
Author(s) -
Lamber Ekaterina P,
Vanhille Laurent,
Textor Larissa C,
Kachalova Galina S,
Sieweke Michael H,
Wilmanns Matthias
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.117
Subject(s) - biology , transcription factor , genetics , dna , dna binding protein , transcription (linguistics) , microbiology and biotechnology , gene , linguistics , philosophy
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.