1. Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor.
- Author
-
Yang F, Agulian T, Sudati JE, Rhoads DB, and Levitsky LL
- Subjects
- Animals, Animals, Suckling, Apoptosis, Base Sequence, Binding Sites, Blotting, Northern, Blotting, Western, Carcinoma, Hepatocellular metabolism, Cell Differentiation, Cell Division, Cell Nucleus metabolism, DNA Mutational Analysis, Early Growth Response Protein 1, Galactokinase genetics, Galactokinase metabolism, Hepatocytes metabolism, Humans, Immunohistochemistry, Mice, Molecular Sequence Data, Mutation, Plasmids metabolism, Point Mutation, Promoter Regions, Genetic, Protein Binding, RNA metabolism, RNA, Messenger metabolism, Stress, Physiological, Time Factors, Transfection, Zinc Fingers, DNA-Binding Proteins biosynthesis, Galactokinase biosynthesis, Gene Expression Regulation, Developmental, Immediate-Early Proteins biosynthesis, Liver enzymology, Transcription Factors biosynthesis
- Abstract
The numerous changes in metabolic pathways that accompany liver development entail associated changes in gene expression. Egr-1 is a zinc-finger transcription factor that regulates genes involved in cellular growth, differentiation, stress response, and apoptosis in many cell types. Egr-1 is induced in liver regeneration in rodents, but its role in normal hepatocyte function has not been characterized. We examined the developmental expression of Egr-1 in mouse liver and found that its expression increased during the suckling period. In screening the sequences of the genes involved in lactose assimilation, we found that the galactokinase gene Glk contains four potential Egr-1 binding sites in its proximal promoter. A minimal promoter of 155 nucleotides encompassing the four Egr-1 sites exhibited activity in hepatoma cell lines by transient transfection assays. Moreover, co-transfection of an Egr-1 expression plasmid increased promoter activity. Finally, mutations introduced into three of the four Egr-1 binding sites decreased activity, whereas mutation of the remaining site increased promoter activity. These data tie Egr-1 and galactokinase together in a developmentally regulated chain to prepare the neonate for suckling.
- Published
- 2004
- Full Text
- View/download PDF