Pax-6 and Cdx-2/3 interact to activate glucagon gene expression on the G1 control element.
J Biol Chem
; 274(7): 4124-32, 1999 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-9933606
ABSTRACT
The promoter element G1, critical for alpha-cell-specific expression of the glucagon gene, contains two AT-rich sequences important for transcriptional activity. Pax-6, a paired homeodomain protein previously shown to be required for normal alpha-cell development and to interact with the enhancer element G3 of the glucagon gene, binds as a monomer to the distal AT-rich site of G1. However, although the paired domain of Pax-6 is sufficient for interaction with the G3 element, the paired domain and the homeodomain are required for high affinity binding to G1. In addition to monomer formation, Pax-6 interacts with Cdx-2/3, a caudal-related homeodomain protein binding to the proximal AT-rich site, to form a heterodimer on G1. Both proteins are capable of directly interacting in the absence of DNA. In BHK-21 cells, Pax-6 activates glucagon gene transcription both through G3 and G1, and heterodimerization with Cdx-2/3 on G1 leads to more than additive transcriptional activation. In glucagon-producing cells, both G1 and G3 are critical for basal transcription, and the Pax-6 and Cdx-2/3 binding sites are required for activation. We conclude that Pax-6 is not only critical for alpha-cell development but also for glucagon gene transcription by its independent interaction with the two DNA control elements, G1 and G3.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Glucagon
/
Regulação da Expressão Gênica
/
Regiões Promotoras Genéticas
/
Proteínas de Homeodomínio
/
Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1999
Tipo de documento:
Article