The activity of the activation function 2 of the human hepatocyte nuclear factor 4 (HNF-4alpha) is differently modulated by F domains from various origins
| Autor: | Suaud, L, Formstecher, P, Laine, B |
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| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Transcriptional Activation
Binding Sites Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Recombinant Fusion Proteins Molecular Sequence Data Phosphoproteins Transfection digestive system Protein Structure Secondary Cell Line DNA-Binding Proteins Nuclear Receptor Coactivator 2 Hepatocyte Nuclear Factor 4 Genes Reporter embryonic structures Trans-Activators Animals Humans Protein Isoforms Amino Acid Sequence Promoter Regions Genetic Research Article Protein Binding Sequence Deletion Transcription Factors |
| Popis: | Hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear hormone-receptor superfamily, which plays an important role in the regulation of several genes involved in numerous metabolic pathways. HNF-4 contains a DNA-binding domain located in domain C and two activation-function domains, designated AF-1 and AF-2, located in domains A/B and E, respectively. The seven isoforms of human HNF-4, termed alpha1-alpha6 and gamma, differ mainly by their A/B and F domains. The high sequence variability of the F domain led us to investigate whether this domain modulates the transcriptional activity of HNF-4. Using constructs having the same core receptor and different F domains, we observed that the F domains of HNF-4 modulate the transactivating activity of the full-length HNF-4. A more precise analysis using HNF-4alpha AF-2 fused to GAL4 protein and various F domains demonstrated that F domains of isoforms alpha3 and gamma exhibited inhibitory effects on the activation function AF-2 but that their inhibition behaviours were weaker than that of HNF-4alpha2 F domain, which has been reported previously. The presence of domain F results in a decreased interaction with the co-activator glucocorticoid receptor-interacting protein 1. For a given F domain, the modulating effects on the full-length HNF-4 as well as on the AF-2 depended on the target promoters. Our results suggest that the presence of domain F results in conformation changes in HNF-4 AF-2 or in its spatial environment, which probably modify the interaction of the AF-2 activation domain with co-factors and transcription factors bound to cis-elements of the target promoters. |
| Databáze: | OpenAIRE |
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