Gene Symbol: HNF4A
Description: hepatocyte nuclear factor 4 alpha
Alias: FRTS4, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha, MODY, MODY1, NR2A1, NR2A21, TCF, TCF14, hepatocyte nuclear factor 4-alpha, HNF4alpha10/11/12, TCF-14, hepatic nuclear factor 4 alpha, nuclear receptor subfamily 2 group A member 1, transcription factor 14, transcription factor HNF-4
Species: human
Products:     HNF4A

Top Publications

  1. Yu X, Mertz J. Distinct modes of regulation of transcription of hepatitis B virus by the nuclear receptors HNF4alpha and COUP-TF1. J Virol. 2003;77:2489-99 pubmed
    To study the effects of the nuclear receptors (NRs) HNF4alpha and COUP-TF1 on the life cycle of hepatitis B virus (HBV), the human hepatoma cell line Huh7 was transiently cotransfected with plasmids containing the HBV genome and encoding ..
  2. Barroso I, Luan J, Wheeler E, Whittaker P, Wasson J, Zeggini E, et al. Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies. Diabetes. 2008;57:3161-5 pubmed publisher
    Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they ..
  3. Boyd M, Bressendorff S, Møller J, Olsen J, Troelsen J. Mapping of HNF4alpha target genes in intestinal epithelial cells. BMC Gastroenterol. 2009;9:68 pubmed publisher
    The role of HNF4alpha has been extensively studied in hepatocytes and pancreatic beta-cells, and HNF4alpha is also regarded as a key regulator of intestinal epithelial cell differentiation...
  4. Jiang G, Nepomuceno L, Hopkins K, Sladek F. Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors. Mol Cell Biol. 1995;15:5131-43 pubmed
    ..These findings lead us to propose that HNF-4 defines a new subclass of nuclear receptors which reside primarily in the nucleus and which bind DNA and regulate transcription as homodimers. ..
  5. Gloyn A, Ellard S, Shepherd M, Howell R, Parry E, Jefferson A, et al. Maturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene. Diabetes. 2002;51:2329-33 pubmed
    ..20 break point, 20q12, is within the region of one of the known MODY genes, hepatocyte nuclear factor-4alpha (HNF4A)...
  6. Kardassis D, Pardali K, Zannis V. SMAD proteins transactivate the human ApoCIII promoter by interacting physically and functionally with hepatocyte nuclear factor 4. J Biol Chem. 2000;275:41405-14 pubmed
  7. Argyrokastritis A, Kamakari S, Kapsetaki M, Kritis A, Talianidis I, Moschonas N. Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17. Hum Genet. 1997;99:233-6 pubmed
    ..hHFN-4 maps to chromosome 20 in a region syntenic with mouse chromosome 2 where the hnf-4 homologue has been assigned. ..
  8. Vaxillaire M, Dina C, Lobbens S, Dechaume A, Vasseur Delannoy V, Helbecque N, et al. Effect of common polymorphisms in the HNF4alpha promoter on susceptibility to type 2 diabetes in the French Caucasian population. Diabetologia. 2005;48:440-4 pubmed
    ..and 686 normoglycaemic subjects, and for linkage in 148 diabetic families in whom significant linkage to the HNF4alpha region had been shown...
  9. Stanescu D, Hughes N, Kaplan B, Stanley C, De Leon D. Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab. 2012;97:E2026-30 pubmed publisher
    Inactivating mutations in HNF1A and HNF4A cause the maturity-onset diabetes of youth (MODY)-3 and MODY1 forms of monogenic diabetes, respectively...

More Information

Publications113 found, 100 shown here

  1. Pascussi J, Robert A, Moreau A, Ramos J, Bioulac Sage P, Navarro F, et al. Differential regulation of constitutive androstane receptor expression by hepatocyte nuclear factor4alpha isoforms. Hepatology. 2007;45:1146-53 pubmed
    ..hepatocytes, electromobility shift and cotransfection assays, we identified a functional and species-conserved HNF4alpha response element (DR1: ccAGGCCTtTGCCCTga) at nucleotide -144...
  2. Weedon M, Owen K, Shields B, Hitman G, Walker M, McCarthy M, et al. Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. Diabetes. 2004;53:3002-6 pubmed
    ..Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young...
  3. Huang J, Levitsky L, Rhoads D. Novel P2 promoter-derived HNF4alpha isoforms with different N-terminus generated by alternate exon insertion. Exp Cell Res. 2009;315:1200-11 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a critical transcription factor for pancreas and liver development and functions in islet beta cells to maintain glucose homeostasis...
  4. Stoffel M, Duncan S. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci U S A. 1997;94:13209-14 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) plays a critical role in regulating the expression of many genes essential for normal functioning of liver, gut, kidney, and pancreatic islets...
  5. Sumi K, Tanaka T, Uchida A, Magoori K, Urashima Y, Ohashi R, et al. Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8. Mol Cell Biol. 2007;27:4248-60 pubmed
    ..Here, we identified a binding site for hepatocyte nuclear factor 4alpha (HNF4alpha) in the ABCG5/ABCG8 intergenic promoter, through which HNF4alpha strongly activated the expression of a reporter ..
  6. Sookoian S, Gemma C, Pirola C. Influence of hepatocyte nuclear factor 4alpha (HNF4alpha) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals. Mol Genet Metab. 2010;99:80-9 pubmed publisher
    The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes...
  7. Kritis A, Argyrokastritis A, Moschonas N, Power S, Katrakili N, Zannis V, et al. Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4. Gene. 1996;173:275-80 pubmed
  8. Flanagan S, Kapoor R, Mali G, Cody D, Murphy N, Schwahn B, et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol. 2010;162:987-92 pubmed publisher
    The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY)...
  9. Barbier O, Girard H, Inoue Y, Duez H, Villeneuve L, Kamiya A, et al. Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4alpha. Mol Pharmacol. 2005;67:241-9 pubmed
    ..Liver-specific disruption of the HNF4alpha gene in mice drastically decreases liver UGT1A9 mRNA levels...
  10. Torres Padilla M, Sladek F, Weiss M. Developmentally regulated N-terminal variants of the nuclear receptor hepatocyte nuclear factor 4alpha mediate multiple interactions through coactivator and corepressor-histone deacetylase complexes. J Biol Chem. 2002;277:44677-87 pubmed
    ..Possible physiological consequences of the multiple interactions with these coregulators are discussed. ..
  11. Winckler W, Weedon M, Graham R, McCarroll S, Purcell S, Almgren P, et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes. 2007;56:685-93 pubmed
    ..12 and a P value <10(-6) in >15,000 samples. We combined these results with our previous studies on HNF4alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 ..
  12. de Boussac H, Ratajewski M, Sachrajda I, Koblos G, Tordai A, Pulaski L, et al. The ERK1/2-hepatocyte nuclear factor 4alpha axis regulates human ABCC6 gene expression in hepatocytes. J Biol Chem. 2010;285:22800-8 pubmed publisher
    ..the tissue-specific expression pattern to the gene and with a putative hepatocyte nuclear factor 4alpha (HNF4alpha) binding site...
  13. Wisely G, Miller A, Davis R, Thornquest A, Johnson R, Spitzer T, et al. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure. 2002;10:1225-34 pubmed
    ..GC/MS and NMR analysis of chloroform/methanol extracts from purified HNF4alpha and HNF4gamma LBDs identified mixtures of saturated and cis-monounsaturated C14-18 fatty acids...
  14. Tanahashi T, Osabe D, Nomura K, Shinohara S, Kato H, Ichiishi E, et al. Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese. Hum Genet. 2006;120:527-42 pubmed
    ..31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4alpha (HNF4alpha). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples...
  15. Nedumaran B, Hong S, Xie Y, Kim Y, Seo W, Lee M, et al. DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression. J Biol Chem. 2009;284:27511-23 pubmed publisher
    ..b>HNF4alpha (hepatocyte nuclear factor 4alpha) is a liver-enriched transcription factor that controls the expression of a ..
  16. Pearson E, Boj S, Steele A, Barrett T, Stals K, Shield J, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007;4:e118 pubmed
    ..hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4alpha) and HNF1A/TCF1 (encoding HNF-1alpha), and the effect of pancreatic deletion of Hnf4a on ..
  17. Peignon G, Thenet S, Schreider C, Fouquet S, Ribeiro A, Dussaulx E, et al. E-cadherin-dependent transcriptional control of apolipoprotein A-IV gene expression in intestinal epithelial cells: a role for the hepatic nuclear factor 4. J Biol Chem. 2006;281:3560-8 pubmed
    ..Altogether, our results suggest that E-cadherin controls enterocyte-specific expression of genes, such as the apoA-IV gene, through the control of hepatic nuclear factor 4alpha nuclear abundance. ..
  18. Iwahashi H, Yamagata K, Yoshiuchi I, Terasaki J, Yang Q, Fukui K, et al. Thyroid hormone receptor interacting protein 3 (trip3) is a novel coactivator of hepatocyte nuclear factor-4alpha. Diabetes. 2002;51:910-4 pubmed
    ..nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load...
  19. Marcil V, Seidman E, Sinnett D, Boudreau F, Gendron F, Beaulieu J, et al. Modification in oxidative stress, inflammation, and lipoprotein assembly in response to hepatocyte nuclear factor 4alpha knockdown in intestinal epithelial cells. J Biol Chem. 2010;285:40448-60 pubmed publisher
    ..To this end, the HNF4A gene was knocked down by transfecting Caco-2 cells with a pGFP-V-RS lentiviral vector containing an shRNA against ..
  20. Aguilera E, Casamitjana R, Ercilla G, Oriola J, Nicoletti F, Gomis R, et al. Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies. Diabet Med. 2005;22:137-43 pubmed
    ..Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D. ..
  21. Niehof M, Borlak J. HNF4 alpha and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes. 2008;57:1069-77 pubmed publisher
    The nuclear receptor hepatic nuclear factor 4 alpha (HNF 4 alpha) is a master regulatory protein and an essential player in the control of a wide range of metabolic processes...
  22. Colclough K, Bellanne Chantelot C, Saint Martin C, Flanagan S, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat. 2013;34:669-85 pubmed publisher
    ..The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor-4 alpha are a rarer cause of MODY with 103 different mutations reported in ..
  23. Reddy S, Yang W, Taylor D, Shen X, Oxender D, Kust G, et al. Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4. J Biol Chem. 1999;274:33050-6 pubmed
    ..The major protein binding to this site was identified as the nuclear hormone receptor HNF4. An increase in HNF4 mRNA and protein levels was observed in HepG2 cells after treatment with PD98059, indicating ..
  24. Pearson E, Pruhova S, Tack C, Johansen A, Castleden H, Lumb P, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia. 2005;48:878-85 pubmed
    ..the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families...
  25. Kamiyama Y, Matsubara T, Yoshinari K, Nagata K, Kamimura H, Yamazoe Y. Role of human hepatocyte nuclear factor 4alpha in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet. 2007;22:287-98 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is an important transcription factor in hepatic gene expression...
  26. Barroso I, Luan J, Middelberg R, Harding A, Franks P, Jakes R, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol. 2003;1:E20 pubmed
    ..2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both ..
  27. Love Gregory L, Permutt M. HNF4A genetic variants: role in diabetes. Curr Opin Clin Nutr Metab Care. 2007;10:397-402 pubmed
    Variants in the hepatocyte nuclear factor 4alpha (HNF4A) gene play a role in the development of diabetes mellitus...
  28. Zhang Y, Bonzo J, Gonzalez F, Wang L. Diurnal regulation of the early growth response 1 (Egr-1) protein expression by hepatocyte nuclear factor 4alpha (HNF4alpha) and small heterodimer partner (SHP) cross-talk in liver fibrosis. J Biol Chem. 2011;286:29635-43 pubmed publisher
    ..Hepatocyte nuclear factor 4α (HNF4α) activated the Egr-1 promoter through three DR1 response elements as identified by trans-activation assays...
  29. Bagwell A, Bento J, Mychaleckyj J, Freedman B, Langefeld C, Bowden D. Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes. Diabetes. 2005;54:1185-90 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4A), the gene for the maturity-onset diabetes of the young type 1 monogenic form of type 2 diabetes, is within the type 2 diabetes-linked region on chromosome 20q12-q13...
  30. Ozeki T, Takahashi Y, Nakayama K, Funayama M, Nagashima K, Kodama T, et al. Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers. Pharmacogenetics. 2003;13:49-53 pubmed
    ..These results suggest that the expression level of DD4 mRNA is cooperatively regulated by the amounts of HNF-1 alpha, HNF-4 alpha and HNF-4 gamma. ..
  31. Wang Z, Burke P. Effects of hepatocyte nuclear factor-4alpha on the regulation of the hepatic acute phase response. J Mol Biol. 2007;371:323-35 pubmed
  32. Takegoshi S, Jiang S, Ohashi R, Savchenko A, Iwanari H, Tanaka T, et al. Protein expression of nuclear receptors in human and murine tissues. Pathol Int. 2009;59:61-72 pubmed publisher
    ..The P2 promoter-driven hepatocyte nuclear factor 4alpha (HNF4alpha) isoform and progesterone receptor were expressed in pancreatic alpha-cells, but not beta-cells in the human ..
  33. Dell H, Hadzopoulou Cladaras M. CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression. J Biol Chem. 1999;274:9013-21 pubmed
    ..These findings demonstrate that CBP acts as a transcriptional coactivator for HNF-4 and provide new insights into the regulatory function of HNF-4. ..
  34. Lehman D, Richardson D, Jenkinson C, Hunt K, Dyer T, Leach R, et al. P2 promoter variants of the hepatocyte nuclear factor 4alpha gene are associated with type 2 diabetes in Mexican Americans. Diabetes. 2007;56:513-7 pubmed
    Common and rare variants of the hepatocyte nuclear factor 4alpha (HNF4A) gene have been associated with type 2 diabetes and related traits in several populations suggesting the involvement of this transcription factor in diabetes ..
  35. Hara K, Horikoshi M, Kitazato H, Ito C, Noda M, Ohashi J, et al. Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type 2 diabetes in the Japanese population. Diabetes. 2006;55:1260-4 pubmed
    ..type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene is located...
  36. Raeder H, Bjørkhaug L, Johansson S, Mangseth K, Sagen J, Hunting A, et al. A hepatocyte nuclear factor-4 alpha gene (HNF4A) P2 promoter haplotype linked with late-onset diabetes: studies of HNF4A variants in the Norwegian MODY registry. Diabetes. 2006;55:1899-903 pubmed
    Variants in hepatocyte nuclear factor (HNF)-4alpha cause maturity-onset diabetes of the young, type 1 (MODY1) and may also be risk factors for type 2 diabetes...
  37. Niehof M, Borlak J. EPS15R, TASP1, and PRPF3 are novel disease candidate genes targeted by HNF4alpha splice variants in hepatocellular carcinomas. Gastroenterology. 2008;134:1191-202 pubmed publisher
    The orphan nuclear receptor HNF4alpha is a member of the hepatic transcription factor network. This protein plays a pivotal role in liver development and hepatocellular differentiation...
  38. Wang F, Han X, Ren Q, Zhang X, Han L, Luo Y, et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J (Engl). 2009;122:2477-82 pubmed
    KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds...
  39. Chellappa K, Jankova L, Schnabl J, Pan S, Brelivet Y, Fung C, et al. Src tyrosine kinase phosphorylation of nuclear receptor HNF4? correlates with isoform-specific loss of HNF4? in human colon cancer. Proc Natl Acad Sci U S A. 2012;109:2302-7 pubmed publisher
    ..The nuclear receptor hepatocyte nuclear factor 4? (HNF4?) has just recently been implicated in colon cancer but its role is poorly defined...
  40. Maeda Y, Rachez C, Hawel L, Byus C, Freedman L, Sladek F. Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205. Mol Endocrinol. 2002;16:1502-10 pubmed
    ..remains a mystery, as does the mechanism by which orphan receptors such as hepatocyte nuclear factor 4alpha (HNF4alpha) activate transcription...
  41. Hirokane H, Nakahara M, Tachibana S, Shimizu M, Sato R. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J Biol Chem. 2004;279:45685-92 pubmed
    ..These results indicate that two nuclear receptors, HNF-4 and FXR, are closely involved in MTP gene expression, and the results provide evidence for a novel interaction between bile acids and lipoprotein metabolism. ..
  42. Muller Y, Infante A, Hanson R, Love Gregory L, Knowler W, Bogardus C, et al. Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians. Diabetes. 2005;54:3035-9 pubmed
    Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4alpha (HNF4alpha) gene are associated with type 2 diabetes in Finns and Ashkenazi Jews...
  43. Møller A, Urhammer S, Dalgaard L, Reneland R, Berglund L, Hansen T, et al. Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM. Diabetologia. 1997;40:980-3 pubmed
    ..hepatocyte nuclear factor-4alpha (HNF-4alpha) gene cause the type 1 form of maturity onset diabetes of the young (MODY1)...
  44. Bonnycastle L, Willer C, Conneely K, Jackson A, Burrill C, Watanabe R, et al. Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes. 2006;55:2534-40 pubmed
    ..To complement our previous studies of HNF4A, we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals...
  45. Qi L, van Dam R, Asselbergs F, Hu F. Gene-gene interactions between HNF4A and KCNJ11 in predicting Type 2 diabetes in women. Diabet Med. 2007;24:1187-91 pubmed
    Recent studies indicate transcription factor hepatocyte nuclear factor 4 alpha (HNF-4 alpha, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ (KATP) channel subunit Kir6.2 gene (KCNJ11)...
  46. Wang Z, Bishop E, Burke P. Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4?. BMC Genomics. 2011;12:128 pubmed publisher
    Hepatocyte nuclear factor 4? (HNF4?), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response...
  47. Chavali S, Mahajan A, Tabassum R, Dwivedi O, Chauhan G, Ghosh S, et al. Association of variants in genes involved in pancreatic ?-cell development and function with type 2 diabetes in North Indians. J Hum Genet. 2011;56:695-700 pubmed publisher
    ..We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6...
  48. Wang J, STAFFORD J, Granner D. SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. J Biol Chem. 1998;273:30847-30850 pubmed
    ..Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene...
  49. Lee Y, Dell H, Dowhan D, Hadzopoulou Cladaras M, Moore D. The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression. Mol Cell Biol. 2000;20:187-95 pubmed
    ..Overall, these results suggest that SHP represses nuclear hormone receptor-mediated transactivation via two separate steps: first by competition with coactivators and then by direct effects of its transcriptional repressor function. ..
  50. You M, Fischer M, Cho W, Crabb D. Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors. Arch Biochem Biophys. 2002;398:79-86 pubmed
    ..regulatory element (designated FP330-3') of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4)...
  51. Song K, Li T, Chiang J. A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene. J Biol Chem. 2006;281:10081-8 pubmed
    ..a specific interaction between the N-terminal LXXLL motif of Prox1 and the activation function 2 domain of HNF4alpha. Prox1 strongly inhibited HNF4alpha and peroxisome proliferators-activated receptor gamma coactivator-1alpha co-..
  52. Wanic K, Malecki M, Wolkow P, Klupa T, Skupien J, Bobrek J, et al. Polymorphisms in the gene encoding hepatocyte nuclear factor-4alpha and susceptibility to type 2 diabetes in a Polish population. Diabetes Metab. 2006;32:86-8 pubmed
    ..We conclude that both examined polymorphisms in HNF-4alpha are not associated with T2DM and prediabetic phenotypes in Polish Caucasian study groups of this size. ..
  53. Johansson S, Raeder H, Eide S, Midthjell K, Hveem K, Søvik O, et al. Studies in 3,523 Norwegians and meta-analysis in 11,571 subjects indicate that variants in the hepatocyte nuclear factor 4 alpha (HNF4A) P2 region are associated with type 2 diabetes in Scandinavians. Diabetes. 2007;56:3112-7 pubmed
    Recent publications have found an association between common variants near the hepatocyte nuclear factor 4 alpha (HNF4A) P2 promoter and type 2 diabetes in some populations but not in others, and the role for HNF4A in type 2 diabetes has ..
  54. Sanyal S, Båvner A, Haroniti A, Nilsson L, Lundåsen T, Rehnmark S, et al. Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis. Proc Natl Acad Sci U S A. 2007;104:15665-70 pubmed
    ..receptors including the orphan receptors liver receptor homolog 1 (LRH-1), hepatocyte nuclear factor 4alpha (HNF4alpha), small heterodimer partner (SHP), and the bile acid receptor FXR (farnesoid X receptor)...
  55. Ktistaki E, Ktistakis N, Papadogeorgaki E, Talianidis I. Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential. Proc Natl Acad Sci U S A. 1995;92:9876-80 pubmed
    ..The correlation between the intranuclear distribution of HNF-4 and its ability to activate endogenous target genes demonstrates a phosphorylation signal-dependent pathway in the regulation of transcription factor activity. ..
  56. Chartier F, Bossu J, Laudet V, Fruchart J, Laine B. Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. Gene. 1994;147:269-72 pubmed
    ..Sequence analysis revealed that two HNF-4 isoforms are also present in human liver. The complete sequence of the longest human isoform has been established and compared to the rat HNF-4 amino-acid sequences. ..
  57. Yamagata K, Furuta H, Oda N, Kaisaki P, Menzel S, Cox N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature. 1996;384:458-60 pubmed
    ..Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key ..
  58. Soutoglou E, Katrakili N, Talianidis I. Acetylation regulates transcription factor activity at multiple levels. Mol Cell. 2000;5:745-51 pubmed
    ..The results show that acetylation is a key posttranslational modification that may affect several properties of a transcription factor critical for the execution of its biological functions. ..
  59. Odom D, Zizlsperger N, Gordon D, Bell G, Rinaldi N, Murray H, et al. Control of pancreas and liver gene expression by HNF transcription factors. Science. 2004;303:1378-81 pubmed
    ..promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets...
  60. de Lucas S, López Alcorocho J, Bartolome J, Carreno V. Nitric oxide and TGF-beta1 inhibit HNF-4alpha function in HEPG2 cells. Biochem Biophys Res Commun. 2004;321:688-94 pubmed
    ..TGF-beta1 and nitric oxide inhibit HNF-4alpha activity. These findings may explain the loss of liver functions that occurs during fibrosis progression. ..
  61. Grigo K, Wirsing A, Lucas B, Klein Hitpass L, Ryffel G. HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells. Biol Chem. 2008;389:179-87 pubmed publisher
    ..The cell-specific transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha) is down-regulated in RCC and we have shown that HNF4 alpha inhibits cell proliferation ..
  62. Zhou T, Zhang Y, Macchiarulo A, Yang Z, Cellanetti M, Coto E, et al. Novel polymorphisms of nuclear receptor SHP associated with functional and structural changes. J Biol Chem. 2010;285:24871-81 pubmed publisher
    ..and blocked SHP acetylation, which displayed lost repressive activity on its interacting partners ERRgamma and HNF4alpha but not LRH-1. In contrast, G171A increased SHP mRNA and protein expression and maintained normal function...
  63. Saif Ali R, Harun R, Al Jassabi S, Wan Ngah W. Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. Acta Biochim Pol. 2011;58:179-86 pubmed
    This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters...
  64. Drewes T, Senkel S, Holewa B, Ryffel G. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol. 1996;16:925-31 pubmed
    Hepatocyte nuclear factor 4 (HNF4) was first identified as a DNA binding activity in rat liver nuclear extracts...
  65. Pruhova S, Ek J, Lebl J, Sumnik Z, Saudek F, Andel M, et al. Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia. 2003;46:291-5 pubmed
    The aim of this study was to examine the prevalence and nature of mutations in HNF4alpha/MODY1, GCK/MODY2 and HNF-1alpha/MODY3 genes in Czech subjects with clinical diagnosis of MODY...
  66. Hong Y, Varanasi U, Yang W, Leff T. AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem. 2003;278:27495-501 pubmed
    ..The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver,..
  67. Thomas H, Senkel S, Erdmann S, Arndt T, Turan G, Klein Hitpass L, et al. Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line. Nucleic Acids Res. 2004;32:e150 pubmed
    ..Using a clone expressing the HNF6, HNF4alpha and HNF1beta transcription factors at a limited level, we introduced the expression vectors encoding these ..
  68. Lucas B, Grigo K, Erdmann S, Lausen J, Klein Hitpass L, Ryffel G. HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma. Oncogene. 2005;24:6418-31 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue-specific transcription factor known to regulate a large number of genes in hepatocytes and pancreatic beta cells...
  69. Lu P, Rha G, Melikishvili M, Wu G, Adkins B, Fried M, et al. Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product. J Biol Chem. 2008;283:33685-97 pubmed publisher
    b>HNF4alpha (hepatocyte nuclear factor 4alpha) plays an essential role in the development and function of vertebrate organs, including hepatocytes and pancreatic beta-cells by regulating expression of multiple genes involved in organ ..
  70. Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, et al. Proteomic analysis of native hepatocyte nuclear factor-4? (HNF4?) isoforms, phosphorylation status, and interactive cofactors. J Biol Chem. 2011;286:674-86 pubmed publisher
    Hepatocyte nuclear factor-4? (HNF4?, NR2A1) is a nuclear receptor that has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver...
  71. Thanabalasingham G, Pal A, Selwood M, Dudley C, Fisher K, Bingley P, et al. Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care. 2012;35:1206-12 pubmed publisher
    ..type 1 diabetes, we sequenced hepatocyte nuclear factor 1 α (HNF1A) and hepatocyte nuclear factor 4 α (HNF4A) in 20 with residual β-cell function ≥ 3 years from diagnosis (random or glucagon-stimulated C-peptide â..
  72. Marcil V, Sinnett D, Seidman E, Boudreau F, Gendron F, Beaulieu J, et al. Association between genetic variants in the HNF4A gene and childhood-onset Crohn's disease. Genes Immun. 2012;13:556-65 pubmed publisher
    ..Moreover, in a genome-wide association study, the HNF4A locus has been associated with ulcerative colitis...
  73. Malik S, Wallberg A, Kang Y, Roeder R. TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4. Mol Cell Biol. 2002;22:5626-37 pubmed
    ..Finally, recruitment experiments using immobilized templates strongly suggest that the functional consequences of the physical interaction probably are manifested at a postrecruitment step in the activation pathway. ..
  74. Hansen S, Parrizas M, Jensen M, Pruhova S, Ek J, Boj S, et al. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function. J Clin Invest. 2002;110:827-33 pubmed
    ..6 kb upstream from the previously characterized Hnf4alpha promoter (P1)...
  75. Eeckhoute J, Moerman E, Bouckenooghe T, Lukoviak B, Pattou F, Formstecher P, et al. Hepatocyte nuclear factor 4 alpha isoforms originated from the P1 promoter are expressed in human pancreatic beta-cells and exhibit stronger transcriptional potentials than P2 promoter-driven isoforms. Endocrinology. 2003;144:1686-94 pubmed
    ..Mutations in the HNF4 alpha gene are correlated with maturity-onset diabetes of the young 1...
  76. Love Gregory L, Wasson J, Ma J, Jin C, Glaser B, Suarez B, et al. A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an ashkenazi jewish population. Diabetes. 2004;53:1134-40 pubmed
    Variants in hepatocyte nuclear factor-4 alpha (HNF4 alpha), a transcription factor that influences the expression of glucose metabolic genes, have been correlated with maturity-onset diabetes of the young, a monogenic form of diabetes...
  77. Damcott C, Hoppman N, Ott S, Reinhart L, Wang J, Pollin T, et al. Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are associated with type 2 diabetes in the Amish. Diabetes. 2004;53:3337-41 pubmed
    Hepatocyte nuclear factor 4-alpha (HNF4A) is a transcription factor located on chromosome 20q13 that regulates expression of genes involved in glucose metabolism and homeostasis...
  78. Hansen S, Rose C, Glumer C, Drivsholm T, Borch Johnsen K, Jørgensen T, et al. Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population. Diabetologia. 2005;48:452-8 pubmed
    ..The gene encoding HNF-4alpha (HNF4A) is located on chromosome 20q12-q13 in a region that in several studies has shown linkage with type 2 diabetes...
  79. Andrulionyte L, Laukkanen O, Chiasson J, Laakso M. Single nucleotide polymorphisms of the HNF4alpha gene are associated with the conversion to type 2 diabetes mellitus: the STOP-NIDDM trial. J Mol Med (Berl). 2006;84:701-8 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a transcription factor, which is necessary for normal function of human liver and pancreatic islets...
  80. Hanniman E, Lambert G, Inoue Y, Gonzalez F, Sinal C. Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. J Lipid Res. 2006;47:2503-14 pubmed
    ..Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. ..
  81. Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides G, Jaeger S, et al. An HNF4?-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell. 2011;147:1233-47 pubmed publisher
    Hepatocyte nuclear factor 4? (HNF4?) is essential for liver development and hepatocyte function...
  82. Boj S, Parrizas M, Maestro M, Ferrer J. A transcription factor regulatory circuit in differentiated pancreatic cells. Proc Natl Acad Sci U S A. 2001;98:14481-6 pubmed
    ..In hepatocytes, hnf4alpha controls the transcription of hnf1alpha, suggesting that this same interaction may operate in beta cells and ..
  83. Chou W, Prokova V, Shiraishi K, Valcourt U, Moustakas A, Hadzopoulou Cladaras M, et al. Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4. Mol Biol Cell. 2003;14:1279-94 pubmed
    ..Furthermore, the specificity of this interaction for certain target promoters may play an important role in various hepatocyte functions, which are regulated by TGFbeta and the Smads. ..
  84. Winckler W, Graham R, de Bakker P, Sun M, Almgren P, Tuomi T, et al. Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 people. Diabetes. 2005;54:886-92 pubmed
    ..reported association of common polymorphisms in the P2 promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with risk for type 2 diabetes...
  85. Weissglas Volkov D, Huertas Vazquez A, Suviolahti E, Lee J, Plaisier C, Canizales Quinteros S, et al. Common hepatic nuclear factor-4alpha variants are associated with high serum lipid levels and the metabolic syndrome. Diabetes. 2006;55:1970-7 pubmed
    ..The HNF-4alpha gene (HNF4A) resides on chromosome 20q12-q13...
  86. Fajans S, Bell G. Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha (HNF4A). Diabetologia. 2007;50:2600-1 pubmed
  87. Kapoor R, Locke J, Colclough K, Wales J, Conn J, Hattersley A, et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes. 2008;57:1659-63 pubmed publisher
    Mutations in the human HNF4A gene encoding the hepatocyte nuclear factor (HNF)-4alpha are known to cause maturity-onset diabetes of the young (MODY), which is characterized by autosomal-dominant inheritance and impaired glucose-..
  88. Iwazaki N, Kobayashi K, Morimoto K, Hirano M, Kawashima S, Furihata T, et al. Involvement of hepatocyte nuclear factor 4 alpha in transcriptional regulation of the human pregnane X receptor gene in the human liver. Drug Metab Pharmacokinet. 2008;23:59-66 pubmed
    ..In this study, we examined the involvement of hepatocyte nuclear factor 4alpha (HNF4alpha; NR2A1) in the transcriptional regulation of the human PXR gene in the human liver...
  89. Wirsing A, Johnstone K, Harries L, Ellard S, Ryffel G, Stanik J, et al. Novel monogenic diabetes mutations in the P2 promoter of the HNF4A gene are associated with impaired function in vitro. Diabet Med. 2010;27:631-5 pubmed publisher
    Mutations in HNF4A cause a form of monogenic beta-cell diabetes...
  90. Jafar Mohammadi B, Groves C, Gjesing A, Herrera B, Winckler W, Stringham H, et al. A role for coding functional variants in HNF4A in type 2 diabetes susceptibility. Diabetologia. 2011;54:111-9 pubmed publisher
    Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes...
  91. Naiki T, Nagaki M, Shidoji Y, Kojima H, Imose M, Kato T, et al. Analysis of gene expression profile induced by hepatocyte nuclear factor 4alpha in hepatoma cells using an oligonucleotide microarray. J Biol Chem. 2002;277:14011-9 pubmed
    ..This cDNA microarray analysis showed that HNF-4alpha is one of the central liver metabolism regulators. ..
  92. Ek J, Rose C, Jensen D, Glümer C, Borch Johnsen K, Jørgensen T, et al. The functional Thr130Ile and Val255Met polymorphisms of the hepatocyte nuclear factor-4alpha (HNF4A): gene associations with type 2 diabetes or altered beta-cell function among Danes. J Clin Endocrinol Metab. 2005;90:3054-9 pubmed
    b>HNF4A encodes an orphan nuclear receptor that plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion...