The HNF1/HNF4-dependent We2 element of woodchuck hepatitis virus controls viral replication and can activate the N-myc2 promoter.
J Virol
; 70(12): 8571-83, 1996 Dec.
Article
em En
| MEDLINE
| ID: mdl-8970982
ABSTRACT
Transcriptional activation of myc family proto-oncogenes through the insertion of viral sequences is the predominant mechanism by which woodchuck hepatitis virus (WHV) induces liver tumors in chronically infected animals. The main target is N-myc2, a functional retroposon of the N-myc gene, but c-myc and N-myc are also marginally involved. Here we identify a major, liver-specific regulatory element in the WHV genome (We2) which efficiently activates the N-myc2 promoter in cultured hepatoma cells. In the context of the episomal viral genome, We2 governs the production of pregenomic RNA and thus plays a central role in the control of viral replication. We2 activity is primarily controlled by the liver-enriched HNF1 and HNF4 transcription factors, although NF1 and Oct proteins were also shown to bind in a central region. The expression of HNF1 and HNF4 appears to be maintained in woodchuck tumors. Thus, We2 is a prime candidate for controlling myc gene cis activation during WHV-induced hepatocarcinogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Fatores de Transcrição
/
Proteínas Nucleares
/
Ativação Transcricional
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Sequências Reguladoras de Ácido Nucleico
/
Proteínas Proto-Oncogênicas c-myc
/
Regiões Promotoras Genéticas
/
Vírus da Hepatite B da Marmota
/
Retroelementos
/
Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
França