A novel retinoic acid-response element requires an enhancer element mediator for transcriptional activation.
Biochem J
; 383(Pt 1): 37-43, 2004 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-15206905
ABSTRACT
The Col11a2 gene codes for alpha2(XI), a subunit of type XI collagen that is a critical component of the cartilage extracellular matrix. The 5' regulatory region of Col11a2 was subjected to deletional analysis to detect any regulatory element in addition to the two known chondrocyte-specific enhancer elements B/C and D/E. Deletion of the region from -342 to -242 bp reduced transcriptional activity to less than 50% of wild-type, but the sequence showed no independent ability to increase transcription from a minimal promoter. When cloned downstream of the D/E enhancer, however, a subsection of the sequence nearly doubled transcriptional activity and produced an additional 3-fold activation in response to RA (retinoic acid). A 6-bp direct repeat, separated by 4 bp (a DR-4 element) near the 5'-end of this region, was found to be essential for its activity, and was further shown to bind the RA X receptor beta in electrophoretic mobility-shift assays. The present study has revealed a novel RA-response element in Col11a2 that does not interact directly with the promoter, but instead requires the D/E enhancer to mediate transcriptional activation. Proteins bound at the enhancer, therefore, would be expected to affect the transcriptional response to RA. Such a system of regulation, particularly if found to be operating in other cartilage genes, could explain the conflicting responses RA produces in chondrocytes under different experimental conditions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Ativação Transcricional
/
Elementos Facilitadores Genéticos
/
Elementos de Resposta
/
Colágeno Tipo XI
Limite:
Animals
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos