The distal enhancer implicated in the developmental regulation of the tyrosine aminotransferase gene is bound by liver-specific and ubiquitous factors.
AUTOR(ES)
Nitsch, D
RESUMO
Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=360060Documentos Relacionados
- Expression from the tyrosine aminotransferase promoter (nt -350 to +1) is liver-specific and dependent on the binding of both liver-enriched and ubiquitous trans-acting factors.
- Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements.
- Developmental appearance of transcription factors that regulate liver-specific expression of the aldolase B gene.
- Binding of a liver-specific factor to the human albumin gene promoter and enhancer.
- Liver-specific expression of hepatitis B virus is determined by the combined action of the core gene promoter and the enhancer.