This table provides an overview of HNF-4 coactivators and agonistic ligands and their functions
| Substance | HNF-4 Domain | Mode of Action | References | |
|---|---|---|---|---|
| Agonistic ligands | Saturated (C14:0)-CoA | LBD | Binding of ligand leads to increased HNF-4α dimerization | Hertz et al., 1998 |
| Binding of ligand activates binding of the HNF-4α dimer to it's cognate enhancer element | ||||
| Saturated (C16:0)-CoA | LBD | Binding of ligand activates binding of the HNF-4α dimer to it's cognate enhancer element | ||
| Coactivators | SRC-1 (NCoA-1) | AF-2 | Specific H3 and H4 histone acetylation by intrinsic SRC-1 HAT activity | Spencer et al., 1997 |
| Interaction with p/CAF (with intrinsic HAT activity) | ||||
| Interaction with C terminus of CBP/p300 (with intrinsic HAT activity) | Yao et al., 1996 | |||
| Interaction between HNF-4, SRC-1, and SRC-2 leading to increased transactivation activity of HNF-4 | Wang et al., 1998a | |||
| SRC-2 (NCoA-2 GRIP1, TIF2) | AF-2 | Interaction between HNF-4, SRC-1, and SRC-2 is leading to increased transactivation activity of HNF-4 | Wang et al., 1998a | |
| SRC-3 (NCoA-3, ACTR, AIB1, p/CIP, TRAM-1, RAC3) | AF-2 | Intrinsic histone acetylase activity | Chen et al., 1997 | |
| Protein-protein interaction with p/CAF and CBP/p300 | Torchia et al., 1997 | |||
| CBP/p300 | AF-1, AF-2 | Interaction between HNF-4 and CBP is ligand-independent. CBP binds to the HNF-4 AF-1 and AF-2 domains with the N terminus and the N and C terminus, respectively | Dell and Hadzopoulou-Cladaras, 1999 | |
| Histone acetylation: intrinsic histone acetylase (HAT) activity | Bannister and Kouzarides, 1996 | |||
| Protein-protein interaction: CBP/p300 binds p/CAF that also contains an intrinsic HAT activity | Yang et al., 1996 | |||
| Acetylation of HNF-4α at lysine residues by CBP/p300 enhances HNF-4α/DNA binding affinity, as well as CBP/p300 binding affinity to HNF-4 and is essential for proper nuclear retention of HNF-4α | Soutoglou et al., 2000a | |||
| Binding to the AF-1 and AF-2 domain leads to ligand-independent HNF-4α activation | Ktistaki et al., 1995 | |||
| CBP/p300 interacts with its N-terminal fragment directly with nuclear receptors, with its C-terminal fragment directly with SRC-1, and with distinct internal regions with CREB, Fos, TFIIB, and E1A | Kamei et al., 1996 | |||
| Acetylation of general transcription factors TFIIEb and TFIIF by p300 leading to increased transcription | Ogryzko et al., 1996 | |||
| Interaction with components of the basal transcription machinery (TBP, TFIIB, RNA helicase) leading to increased transcription | Kamei et al., 1996 | |||
| ADA2 | AF-1 | ADA2-GCN5 complex acetylates histones | Green et al., 1998 | |
| ADA2 interacts with the AF-1 domain of HNF-4 and TBP and TAFs facilitating transcription by the transcriptional machinery | Barlev et al., 1995 | |||
| PC4 | AF-1 | PC4 contains two ssDNA binding domains that might be implicated in the opening of the DNA double helix at a post-initiation step | Green et al., 1998; Brandsen et al., 1997 | |
| PC4 interacts with the AF-1 domain of HNF-4 and TAFs facilitating transcription by the transcriptional machinery | Ge and Roeder, 1994 | |||
| COUP-TFI/COUP-TFII | E | Promoters that are recognized by HNF-4a and not by COUP-TFs lead to a coactivator function of COUP-TFs through a protein/protein interaction between HNF-4 and COUP-TFs at the HNF-4 E domain | Ktistaki and Talianidis, 1997 |