Table 4

This table provides an overview of HNF-4 coactivators and agonistic ligands and their functions

SubstanceHNF-4 DomainMode of ActionReferences
Agonistic ligandsSaturated (C14:0)-CoALBDBinding 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)-CoALBDBinding of ligand activates binding of the HNF-4α dimer to it's cognate enhancer element
CoactivatorsSRC-1 (NCoA-1)AF-2Specific 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-2Interaction 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-2Intrinsic histone acetylase activity Chen et al., 1997
Protein-protein interaction with p/CAF and CBP/p300 Torchia et al., 1997
CBP/p300AF-1, AF-2Interaction 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
ADA2AF-1ADA2-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
PC4AF-1PC4 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-TFIIEPromoters 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