Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization.
EMBO J
; 27(14): 2006-17, 2008 Jul 23.
Article
em En
| MEDLINE
| ID: mdl-18566588
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Regiões Promotoras Genéticas
/
Metaloproteinase 3 da Matriz
/
Proteína Proto-Oncogênica c-ets-1
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2008
Tipo de documento:
Article