Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1.
Biochem Biophys Res Commun
; 333(4): 1361-9, 2005 Aug 12.
Article
em En
| MEDLINE
| ID: mdl-15982639
ABSTRACT
Mixl1 is a paired-type homeodomain protein that plays a crucial role in morphogenesis and endoderm differentiation in the murine embryo. To understand how Mixl1 directs embryogenesis, we studied the regulation of Mixl1 expression at a transcriptional level. In HepG2 cells, a genomic fragment encompassing the Mixl1 promoter conferred strong TGF-beta-induced transcription that was dependent on the presence of the DNA-binding protein FoxH1. Further analysis of the Mixl1 promoter identified a proximal response element (PRE) containing SMAD- and FoxH1-binding sites required for TGF-beta responsiveness. The PRE was also responsive to signalling by Nodal, a TGF-beta ligand required for normal embryonic patterning. These results demonstrate for the first time a functional role for TGF-beta ligands in regulation of mammalian Mixl1, identify FoxH1 as an essential transcriptional co-activator, and implicate Nodal as the embryonic regulator of Mixl1 in mesendoderm morphogenesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Ativação Transcricional
/
Fator de Crescimento Transformador beta
/
Proteínas de Homeodomínio
/
Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Austrália