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 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
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Overview

HNF4α1 is expressed in liver (hepatocytes), kidney (proximal tubules), small intestine, colon and pancreas (beta cells), although hepatocytes remain one of the highest expressing cell types [1]. HNF4α2 is the most predominant isoform in adult liver and the kidney; both are driven by the P1 promoter. (Early papers that do not explicitly specify the isoform all used HNF4α1). HNF4α7/8 is not present in the adult liver or kidney but is the most predominant form in the beta cells of the pancreas. It is also expressed in the small intestine and colon along with HNF4α1/2.The level of HNF4α mRNA and hence protein in the liver is regulated by a variety of physiological and pathological conditions, including fasting which increases HNF4α levels and hyperinsulinemia which decreases HNF4α levels, at least in part via the SREBP transcription factors [2].

There are also reports of HNF4α in the stomach [3][4], non beta cell compartments of the pancreas [5] as well as the mammary epithelium [6]and ovarian cancer [7], although the role of HNF4α in those tissues has not been elucidated.

HNF4α is expressed in many but not all human and rodent cell lines of hepatic, colonic and beta cell origin. The level of expression varies among the cell lines and isolates as does the relative expression of the different HNF4α isoforms; only a few lines have been analyzed for HNF4a3/9 [8].

Transformed cell lines of kidney origin, (e.g. , HEK293, Cos-7, Cos-1) do not express HNF4α.

Primary hepatocytes and beta cells from human, mouse and rat also express HNF4α although the levels are highly dependent on the culture conditions.

Commonly used cell lines expressing HNF4α (based on the authors' and others' observations [3][8]):

  • HepG2 (mainly HNF4α1/2 with lesser amounts of HNF4α7/8)
  • Hep3B (mainly HNF4α1/2, also HNF4α3/9)
  • Huh7 (HNF4α1/2 and HNF4α7/8)
  • H35 (mainly HNF4α1/2)
  • Caco2 (mainly HNF4α7/8 with lesser amounts of HNF4α1/2)
  • Kato III (HNF4α7/8 only)
  • INS-1 (mainly HNF4α7/8, also HNF4α3/9)


Expression profiles from the Nuclear Receptor Atlas (NURSA):

  • [1] - Expression profile of HNF4α in different tissues
  • [2] - Circadian expression of HNF4α

Expression of HNF4α protein in these datasets has not yet been verified.

References
  1. Sladek FM et al. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev., 4(12B):2353-65. (PMID 2279702)
  2. Xie X et al. Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs. Mol. Endocrinol., 23(4):434-43. (PMID 19179483)
  3. Tanaka T et al. Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J. Pathol., 208(5):662-72. (PMID 16400631)
  4. Harries LW et al. The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development. Diabetes, 57(6):1745-52. (PMID 18356407)
  1. Nammo T et al. Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. Gene Expr. Patterns, 8(2):96-106. (PMID 17996499)
  2. Ishikawa F et al. Downregulation of hepatocyte nuclear factor-4alpha and its role in regulation of gene expression by TGF-beta in mammary epithelial cells. Exp. Cell Res., 314(10):2131-40. (PMID 18433744)
  3. Sugai M et al. Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors. Pathol. Int., 58(11):681-6. (PMID 18844932)
  4. Huang J et al. Expression of HNF4alpha variants in pancreatic islets and Ins-1 beta cells. Diabetes Metab. Res. Rev., 24(7):533-43. (PMID 18561282)
Expression (automatically populated)
GNF Expression Atlas 2 Data from U133A and GNF1H Chips
Using GNF ID 216889_s_at that is linked to Ensembl Transcript ID ENST00000372913
1. Fetal brain
-24 
2. Whole brain
-67 
 
3. Temporal lobe
-27 
4. Parietal lobe
-18 
5. Occipital lobe
-48 
6. Prefrontal cortex
47 
7. Cingulate cortex
70 
8. Cerebellum
-5 
9. Cerebellum peduncles
-26 
10. Amygdala
-45 
11. Hypothalamus
6 
12. Thalamus
4 
13. Subthalamic nucleus
-58 
14. Caudate nucleus
30 
15. Globus pallidus
-4 
16. Olfactory bulb
-100 
17. Pons
-25 
18. Medulla oblongata
-26 
 
19. Spinal cord
-57 
20. Ciliary ganglion
-13 
21. Trigeminal ganglion
16 
22. Superior cervical ganglion
-32 
23. Dorsal root ganglion
-46 
 
24. Thymus
-73 
25. Tonsil
-9 
26. Lymph node
14 
27. Bone marrow
41 
28. BM-CD71+ early erythroid
-12 
29. BM-CD33+ myeloid
-16 
30. BM-CD105+ endothelial
59 
31. BM-CD34+
-11 
32. Whole blood
-41 
 
33. PB-BDCA4+ dentritic cells
37 
34. PB-CD14+ monocytes
12 
35. PB-CD56+ NKCells
1 
36. PB-CD4+ Tcells
13 
37. PB-CD8+ Tcells
28 
38. PB-CD19+ Bcells
19 
 
39. Leukemia lymphoblastic (molt4)
9 
40. 721 B lymphoblasts
31 
41. Lymphoma Burkitts Raji
37 
42. Leukemia promyelocytic (hl60)
40 
43. Lymphoma Burkitts Daudi
79 
44. Leukemia chronic myelogenous (k562)
-8 
45. Colorectal adenocarcinoma
8 
 
46. Appendix
65 
47. Skin
-45 
48. Adipocyte
-1 
49. Fetal thyroid
99 
50. Thyroid
12 
51. Pituitary gland
-79 
 
52. Adrenal gland
-30 
53. Adrenal cortex
54 
54. Prostate
17 
55. Salivary gland
13 
56. Pancreas
-7 
57. Pancreatic islets
11 
 
58. Atrioventricular node
10 
59. Heart
49 
60. Cardiac myocytes
41 
61. Skeletal muscle
23 
62. Tongue
-47 
63. Smooth muscle
21 
64. Uterus
12 
65. Uterus corpus
5 
66. Trachea
-6 
 
67. Bronchial epithelial cells
-47 
68. Fetal lung
-87 
69. Lung
-19 
 
70. Kidney
16 
71. Fetal liver
14 
72. Liver
-6 
73. Placenta
-36 
 
74. Testis
-46 
75. Testis Leydig cell
17 
76. Testis germ cell
-27 
77. Testis interstitial
0 
78. Testis seminiferous tubule
-13 
79. Ovary
-18 
GNF Expression Atlas 2 Data from U133A and GNF1H Chips
Using GNF ID 214832_at that is linked to Ensembl Transcript ID ENST00000316099
1. Fetal brain
25 
2. Whole brain
-38 
 
3. Temporal lobe
-13 
4. Parietal lobe
48 
5. Occipital lobe
-38 
6. Prefrontal cortex
8 
7. Cingulate cortex
-39 
8. Cerebellum
-9 
9. Cerebellum peduncles
28 
10. Amygdala
-31 
11. Hypothalamus
-17 
12. Thalamus
0 
13. Subthalamic nucleus
-78 
14. Caudate nucleus
-19 
15. Globus pallidus
-13 
16. Olfactory bulb
-9 
17. Pons
23 
18. Medulla oblongata
-33 
 
19. Spinal cord
-44 
20. Ciliary ganglion
-11 
21. Trigeminal ganglion
30 
22. Superior cervical ganglion
-5 
23. Dorsal root ganglion
-37 
 
24. Thymus
-78 
25. Tonsil
-7 
26. Lymph node
18 
27. Bone marrow
45 
28. BM-CD71+ early erythroid
-30 
29. BM-CD33+ myeloid
0 
30. BM-CD105+ endothelial
-18 
31. BM-CD34+
-38 
32. Whole blood
22 
 
33. PB-BDCA4+ dentritic cells
-47 
34. PB-CD14+ monocytes
-52 
35. PB-CD56+ NKCells
57 
36. PB-CD4+ Tcells
32 
37. PB-CD8+ Tcells
-21 
38. PB-CD19+ Bcells
0 
 
39. Leukemia lymphoblastic (molt4)
-12 
40. 721 B lymphoblasts
-12 
41. Lymphoma Burkitts Raji
71 
42. Leukemia promyelocytic (hl60)
-34 
43. Lymphoma Burkitts Daudi
41 
44. Leukemia chronic myelogenous (k562)
-24 
45. Colorectal adenocarcinoma
39 
 
46. Appendix
-2 
47. Skin
-38 
48. Adipocyte
25 
49. Fetal thyroid
70 
50. Thyroid
8 
51. Pituitary gland
-32 
 
52. Adrenal gland
-45 
53. Adrenal cortex
32 
54. Prostate
24 
55. Salivary gland
-39 
56. Pancreas
-30 
57. Pancreatic islets
9 
 
58. Atrioventricular node
-31 
59. Heart
53 
60. Cardiac myocytes
60 
61. Skeletal muscle
85 
62. Tongue
48 
63. Smooth muscle
9 
64. Uterus
20 
65. Uterus corpus
30 
66. Trachea
-78 
 
67. Bronchial epithelial cells
13 
68. Fetal lung
-44 
69. Lung
37 
 
70. Kidney
-6 
71. Fetal liver
11 
72. Liver
100 
73. Placenta
-8 
 
74. Testis
-6 
75. Testis Leydig cell
14 
76. Testis germ cell
-9 
77. Testis interstitial
18 
78. Testis seminiferous tubule
-52 
79. Ovary
3