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• W2022234846 endingPage "169" @default.
• W2022234846 startingPage "161" @default.
• W2022234846 abstract "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 α1-α6 and γ, 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-4α AF-2 fused to GAL4 protein and various F domains demonstrated that F domains of isoforms α3 and γ exhibited inhibitory effects on the activation function AF-2 but that their inhibition behaviours were weaker than that of HNF-4α2 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." @default.
• W2022234846 created "2016-06-24" @default.
• W2022234846 creator A5057376310 @default.
• W2022234846 creator A5057794804 @default.
• W2022234846 creator A5061086516 @default.
• W2022234846 date "1999-05-10" @default.
• W2022234846 modified "2023-09-25" @default.
• W2022234846 title "The activity of the activation function 2 of the human hepatocyte nuclear factor 4 (HNF-4α) is differently modulated by F domains from various origins" @default.
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• W2022234846 doi "https://doi.org/10.1042/bj3400161" @default.
• W2022234846 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1220234" @default.
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• W2022234846 hasPublicationYear "1999" @default.
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