Conformational stability and DNA binding specificity of the cardiac T-box transcription factor Tbx20.
J Mol Biol
; 389(3): 606-18, 2009 Jun 12.
Article
em En
| MEDLINE
| ID: mdl-19414016
ABSTRACT
The transcription factor Tbx20 acts within a hierarchy of T-box factors in lineage specification and morphogenesis in the mammalian heart and is mutated in congenital heart disease. T-box family members share a approximately 20-kDa DNA-binding domain termed the T-box. The question of how highly homologous T-box proteins achieve differential transcriptional control in heart development, while apparently binding to the same DNA sequence, remains unresolved. Here we show that the optimal DNA recognition sequence for the T-box of Tbx20 corresponds to a T-half-site. Furthermore, we demonstrate using purified recombinant domains that distinct T-boxes show significant differences in the affinity and kinetics of binding and in conformational stability, with the T-box of Tbx20 displaying molten globule character. Our data highlight unique features of Tbx20 and suggest mechanistic ways in which cardiac T-box factors might interact synergistically and/or competitively within the cardiac regulatory network.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Proteínas com Domínio T
/
Miocárdio
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Austrália