Recently visited
Please sign in to see a list of articles you recently visited.
Recently updated
 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
Comments (post)
There are no comments posted here... Yet.
Overview

HNF4α expression and function are regulated by interactions with a variety of different transcription factors, co-regulators, modifying enzymes, etc. The data below were obtained from various species, but due to the highly conserved function and structure of the HNF4α protein and gene, many if not most will be applicable to human HNF4α.

Included in this list are post translational modifications -- HNF4α is heavily phosphorylated as well as methylated and acetylated -- as well as factors that regulate the expression of the HNF4α gene. Unless otherwise noted, it should be assumed that it is the P1 promoter and the HNF4α1/2 isoforms that are being discussed.

The endogenous ligand for HNF4α is the essential fatty acid linoleic acid (C18:2)[1]. While a significant transcriptional function of LA on HNF4α has not yet been observed, other synthetic compounds (nitro-naphthofurans) have been reported to bind the HNF4α ligand binding domain and alter the ability of HNF4α to activate transcription [2].

Key papers on the regulation of the HNF4α gene:

  • Hatzis et al, 2001 [3]
  • Bailly et al, 2001 [4]
  • Braincon et al 2004 [5]
  • Kyrmizi et al, 2006 [6]
References
  1. Yuan X et al. Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS ONE, 4(5):e5609. (PMID 19440305)
  2. Le Guével R et al. Identification of small molecule regulators of the nuclear receptor HNF4alpha based on naphthofuran scaffolds. Bioorg. Med. Chem., 17(19):7021-30. (PMID 19729315)
  3. Hatzis P and Talianidis I. Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol. Cell. Biol., 21(21):7320-30. (PMID 11585914)
  1. Bailly A et al. An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors. Nucleic Acids Res., 29(17):3495-505. (PMID 11522818)
  2. Briançon N et al. Expression of the alpha7 isoform of hepatocyte nuclear factor (HNF) 4 is activated by HNF6/OC-2 and HNF1 and repressed by HNF4alpha1 in the liver. J. Biol. Chem., 279(32):33398-408. (PMID 15159395)
  3. Kyrmizi I et al. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev., 20(16):2293-305. (PMID 16912278)
Ligands (author curated)
  Ligand Experiment Types and Papers Nature of Interaction
1 Linoleic Acid
CID 5280450
Co-purificationUnknown
Interactions (author curated)
  Interactor Experiment Types and Papers Nature of Interaction
1 ACP5 (human)
Not specified
12101254
Physical: with co-activator affecting recruitment
2 Acvr1 (rat)
Not specified
9462689
Regulatory: increases expression of this TF
3 Acvr1 (rat)
Not specified
9462689
Regulatory: increases expression of this TF
4 CBX4 (human)
Not specified
10882111
Physical: with another TF
5 CCNDBP1 (human)
Not specified
10915743
Regulatory: decreases expression of this TF
6 CREBBP (human)
Not specified
10882110
Physical: enzyme modification: acetylation
7 CREBBP (human)
Not specified
10085149
Physical: with co-activator affecting recruitment
8 Crebbp (mouse)
Not specified
12205093
Physical: with co-activator affecting recruitment
9 Ctnnb1 (mouse)
Not specified
18393386
Regulatory: decreases expression of this TF
10 Dbi (rat)
Not specified
14530276
Physical: with another TF
11 Egf (rat)
Not specified
9784420
Regulatory: increases expression of this TF
12 Fgf1 (rat)
Not specified
11017879
Regulatory: decreases expression of this TF
13 Fn1 (rat)
Not specified
10707864
Regulatory: increases expression of this TF
14 Foxa1 (mouse)
Not specified
9685261
Regulatory: decreases expression of this TF
15 Foxa2 (rat)
Not specified
9685261
Regulatory: increases expression of this TF
16 Foxo1 (rat)
Not specified
12519792
Physical: with another TF: complex binds DNA
17 Gata6 (mouse)
Not specified
9832509
Regulatory: increases expression of this TF
18 Gcg (rat)
Not specified
10922486
Regulatory: increases expression of this TF
19 Gh1 (rat)
Not specified
11026552
Regulatory: increases expression of this TF
20 Ghrh (rat)
Not specified
10674400
Regulatory: increases expression of this TF
21 GTF2B (human)
Not specified
9792714
Physical: with another TF
22 GTF2B (human)
Not specified
8657158
Physical: with co-activator affecting recruitment
23 Hgf (rat)
Not specified
9784420
Regulatory: increases expression of this TF
24 Hnf4a (mouse)
Not specified
15159395
Regulatory: increases expression of this TF
25 IFNGR2 (human)
Not specified
11368795
Physical: with another TF
26 IFRD1 (human)
Not specified
9792714
Physical: with another TF
27 IFRD1 (human)
Invitro
17317687
Physical: with co-activator affecting recruitment
28 Il1b (rat)
Not specified
11679969
Physical: enzyme modification: protein cleavage
29 Il1b (rat)
Not specified
9462689
Regulatory: increases expression of this TF
30 Il6 (rat)
Not specified
9462689
Regulatory: increases expression of this TF
31 Ins2 (rat)
Not specified
10922486
Regulatory: decreases expression of this TF
32 MAPK14 (human)
Not specified
17317687
Physical: enzyme modification: phosphorylation
33 MAPK14 (human)
Not specified
17317687
Regulatory: decreases expression of this TF
34 MED1 (human)
Not specified
12101254
Physical: with co-activator affecting recruitment
35 MED1 (human)
Not specified
12089346
Physical: with co-activator affecting recruitment
36 Myc (mouse)
Not specified
17885207
Competitive inhibition
37 MYC (human)
Not specified
17885207
Physical: with another TF
38 NCOA1 (human)
Not specified
9812974
Physical: with co-activator affecting recruitment
39 Ncoa2 (mouse)
Not specified
12205093
Physical: with co-activator affecting recruitment
40 Ncoa2 (mouse)
Not specified
10490591
Physical: with co-activator affecting recruitment
41 Ncoa2 (mouse)
Not specified
9812974
Physical: with co-activator affecting recruitment
42 Ncor2 (mouse)
Not specified
11865043
Physical: with co-activator affecting recruitment
43 NOTCH2 (human)
Not specified
15226394
Regulatory: decreases expression of this TF
44 NR0B1 (human)
Not specified
19651776
Physical: with another TF
45 NR0B2 (human)
Not specified
14672953
Physical: with another TF
46 NR1I2 (human)
Co-purification
15322103
Physical: with another TF
47 NR2F1 (human)
Not specified
10574924
Physical: with co-activator affecting recruitment
48 Nr2f2 (mouse)
Not specified
18474611
Regulatory: increases expression of this TF
49 Nr5a2 (rat)
Not specified
14766742
Competitive inhibition
50 Onecut1 (rat)
Not specified
11026552
Regulatory: increases expression of this TF
51 Onecut1 (rat)
Not specified
15159395
Regulatory: increases expression of this TF
52 Onecut2 (mouse)
Not specified
15159395
Regulatory: increases expression of this TF
53 Osmr (rat)
Not specified
12774017
Regulatory: increases expression of this TF
54 Per2 (mouse)
Invitro
20159955
Physical: with another TF
55 PPARA (human)
Not specified
15067378
Physical: with another TF: complex binds DNA
56 PPARA (human)
Not specified
10744771
Regulatory: decreases expression of this TF
57 Ppargc1a (mouse)
Not specified
11557972
Physical: with co-activator affecting recruitment
58 Ppargc1a (mouse)
Not specified
11557972
Regulatory: increases expression of this TF
59 PRKACA (human)
Not specified
9234678
Physical: enzyme modification: phosphorylation
60 PRKACA (human)
Invitro
9234678
Physical: enzyme modification: phosphorylation
61 Prkcq (mouse)
Not specified
17389749
Physical: enzyme modification: phosphorylation
62 PROX1 (human)
Not specified
16488887
Physical: with co-activator affecting recruitment
63 Rasd1 (rat)
Not specified
10922486, 7626113
Regulatory: increases expression of this TF
64 RB1 (human)
Co-purification
15767262
Physical: with co-activator affecting recruitment
65 RXRA (human)
Not specified
10744771
Regulatory: decreases expression of this TF
66 RXRA (human)
Not specified
11027556
Regulatory: increases expression of this TF
67 SMAD3 (human)
Not specified
12631740
Physical: with co-activator affecting recruitment
68 SMAD4 (human)
Not specified
12631740
Physical: with co-activator affecting recruitment
69 Snai1 (mouse)
Not specified
16826572
Regulatory: decreases expression of this TF
70 Sp1 (mouse)
Not specified
17885207
Physical: with another TF
71 SREBF1 (human)
Not specified
12855700
Physical: with co-activator affecting recruitment
72 Srebf1 (mouse)
Not specified
17636037
Physical: with co-activator affecting recruitment
73 SREBF1 (human)
Not specified
19179483
Regulatory: decreases expression of this TF
74 SREBF2 (human)
Not specified
19179483
Regulatory: decreases expression of this TF
75 TADA2L (human)
Not specified
9792714
Physical: with another TF
76 TAF6 (human)
Not specified
9792714
Physical: with another TF
77 TAF9 (human)
Not specified
9792714
Physical: with another TF
78 TBP (human)
Not specified
9792714
Physical: with another TF
79 Tgfb1 (rat)
Not specified
10527619
Regulatory: decreases expression of this TF
80 Tgfb1 (rat)
Not specified
11017879
Regulatory: decreases expression of this TF
81 Tgfb1 (rat)
Not specified
9462689
Regulatory: increases expression of this TF
82 Tnf (mouse)
Not specified
17463158
Regulatory: decreases expression of this TF
83 TP53 (human)
Not specified
11818510
Competitive inhibition
84 TP53 (human)
Not specified
16895524
Regulatory: decreases expression of this TF
85 VDR (human)
Not specified
19106115
Physical: with another TF
86 Wt1 (rat)
Not specified
12829997
Regulatory: decreases expression of this TF
Interactions (automatically populated)
  Interactor Experiment Types and Papers Nature of Interaction
1 AR Co-localization
12944908
(not specified by author)
2 CREBBP (TF) Reconstituted Complex, Phenotypic Enhancement, Two-hybrid, Affinity Capture-Western
10085149, 9434765
Physical: with co-activator affecting recruitment
Physical: with another TF
3 CTNNB1 Reconstituted Complex, Affinity Capture-Western
12944908
(not specified by author)
4 EXT2 Affinity Capture-MS
17353931
(not specified by author)
5 FOXO1 Reconstituted Complex
12519792
(not specified by author)Specified in other articles:
Not specified
6 MED1 Affinity Capture-Western, Reconstituted Complex
12089346, 12101254
(not specified by author)
7 MED10 Reconstituted Complex
12101254
(not specified by author)
8 MED14 (TF) Affinity Capture-Western, Reconstituted Complex
12089346, 12101254
Physical: with another TF: complex binds DNA
9 MED16 Reconstituted Complex
12101254
(not specified by author)
10 MED17 Reconstituted Complex
12101254
Physical: with co-activator affecting recruitment
11 MED21 Reconstituted Complex
12101254
(not specified by author)
12 MED23 (TF) Affinity Capture-Western
12089346
Physical: with another TF: complex binds DNA
13 MED24 Reconstituted Complex
12101254
(not specified by author)
14 MED7 Reconstituted Complex
12101254
Physical: with co-activator affecting recruitment
15 NCOA1 Two-hybrid
9812974
(not specified by author)
16 NCOA2 Two-hybrid
9812974
(not specified by author)
17 NR0B2 Reconstituted Complex, Two-hybrid
10594021
(not specified by author)
18 NR2C2 Reconstituted Complex, Affinity Capture-Western, Two-hybrid
12522137
(not specified by author)
19 PABPC4 Affinity Capture-MS
17353931
(not specified by author)
20 PPARGC1B Reconstituted Complex
11733490
Physical: with co-activator affecting recruitment
21 RAD50 Affinity Capture-MS
17353931
(not specified by author)
22 SNCG Affinity Capture-MS
17353931
(not specified by author)
23 STK16 Affinity Capture-MS
17353931
(not specified by author)
24 SUB1 Affinity Capture-Western
11741883
Physical: with co-activator affecting recruitment
25 TP53 (TF) Reconstituted Complex
11818510
Physical: with another TF
26 ZNHIT3 (TF) Two-hybrid, Reconstituted Complex
11916906
Physical: with another TF
Transcriptional regulators (automatically populated)
About this section
Data found in this section is cached from PAZAR, a public database of transcription factor and regulatory sequence annotation. Visit PAZAR at http://www.pazar.info/.
  Regulating TF complex Regulating TF Genomic links GO terms (biological process) Pubmed
1
GATA6_HUMAN
TF0000443
GATA6
Homo sapiens
ENSG00000141448
2627 (Entrez Gene)
(no terms found) 11585914
2
ONECUT1_HUMAN
TF0000444
ONECUT1
Homo sapiens
ENSG00000169856
3175 (Entrez Gene)
(no terms found) 11585914
3
TCF1_HUMAN
TF0000357
HNF1A
Homo sapiens
ENSG00000135100
6927 (Entrez Gene)
29 terms found 11585914