HNF4A

Summary

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

Top Publications

  1. pmc Phosphorylation of Ser158 regulates inflammatory redox-dependent hepatocyte nuclear factor-4alpha transcriptional activity
    Hongtao Guo
    Department of Surgery, Duke University Medical Center, Durham, NC 27514, USA
    Biochem J 394:379-87. 2006
  2. pmc Control of pancreas and liver gene expression by HNF transcription factors
    Duncan T Odom
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 303:1378-81. 2004
  3. ncbi 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
    Latisha D Love-Gregory
    Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Diabetes 53:1134-40. 2004
  4. pmc Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function
    Sara K Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    J Clin Invest 110:827-33. 2002
  5. ncbi Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus
    JianPing Weng
    Department of Endocrinology, Malmo University Hospital, Lund University, Malmo, Sweden
    Diabetes Care 25:68-71. 2002
  6. pmc An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis
    Maria Hatziapostolou
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 147:1233-47. 2011
  7. ncbi A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young
    H Thomas
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, Hufelandstrasse 55, D 45122 Essen, Germany
    Hum Mol Genet 10:2089-97. 2001
  8. doi 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
    Kevin Colclough
    Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
    Hum Mutat 34:669-85. 2013
  9. ncbi Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese
    Toshihito Tanahashi
    Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3 18 15, Tokushima, Japan
    Hum Genet 120:527-42. 2006
  10. ncbi Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population
    S K Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, Gentofte, 2820, Copenhagen, Denmark
    Diabetologia 48:452-8. 2005

Detail Information

Publications220 found, 100 shown here

  1. pmc Phosphorylation of Ser158 regulates inflammatory redox-dependent hepatocyte nuclear factor-4alpha transcriptional activity
    Hongtao Guo
    Department of Surgery, Duke University Medical Center, Durham, NC 27514, USA
    Biochem J 394:379-87. 2006
    ..The corresponding transcription factor was identified to be HNF4alpha (hepatocyte nuclear factor-4alpha)...
  2. pmc Control of pancreas and liver gene expression by HNF transcription factors
    Duncan T Odom
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 303:1378-81. 2004
    ..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...
  3. ncbi 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
    Latisha D Love-Gregory
    Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Diabetes 53:1134-40. 2004
    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...
  4. pmc Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function
    Sara K Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    J Clin Invest 110:827-33. 2002
    ..6 kb upstream from the previously characterized Hnf4alpha promoter (P1)...
  5. ncbi Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus
    JianPing Weng
    Department of Endocrinology, Malmo University Hospital, Lund University, Malmo, Sweden
    Diabetes Care 25:68-71. 2002
    To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM).
  6. pmc An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis
    Maria Hatziapostolou
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 147:1233-47. 2011
    Hepatocyte nuclear factor 4α (HNF4α) is essential for liver development and hepatocyte function...
  7. ncbi A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young
    H Thomas
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, Hufelandstrasse 55, D 45122 Essen, Germany
    Hum Mol Genet 10:2089-97. 2001
    ..e. HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5)...
  8. doi 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
    Kevin Colclough
    Department of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
    Hum Mutat 34:669-85. 2013
    ..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 ..
  9. ncbi Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese
    Toshihito Tanahashi
    Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3 18 15, Tokushima, Japan
    Hum Genet 120:527-42. 2006
    ..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...
  10. ncbi Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population
    S K Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, Gentofte, 2820, Copenhagen, Denmark
    Diabetologia 48:452-8. 2005
    ..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...
  11. pmc E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-catenin-Tcf/Lef-dependent transcription
    Vicente A Torres
    FONDAP Center for Molecular Studies of the Cell, Facultad de Medicina, Universidad de Chile, Av Independencia 1027, Santiago, Chile
    Mol Cell Biol 27:7703-17. 2007
    ..of the inhibitor of apoptosis protein survivin via a transcriptional mechanism involving the beta-catenin-Tcf/Lef pathway...
  12. ncbi Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes
    Allison M Bagwell
    Molecular Genetics Program, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Diabetes 54:1185-90. 2005
    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...
  13. pmc A transcription factor regulatory circuit in differentiated pancreatic cells
    S F Boj
    Endocrinology and Hormonal Biochemistry Units, Hospital Clinic Universitari, Institut d Investigacions Biomediques August Pi i Sunyer, Villarroel 170, 08036 Barcelona, Spain
    Proc Natl Acad Sci U S A 98:14481-6. 2001
    ..In hepatocytes, hnf4alpha controls the transcription of hnf1alpha, suggesting that this same interaction may operate in beta cells and ..
  14. pmc NR2F1 disrupts synergistic activation of the MTTP gene transcription by HNF-4α and HNF-1α
    Kezhi Dai
    Departments of Cell Biology and Pediatrics, Program of Molecular and Cellular Biology, School of Graduate Studies, SUNY Downstate Medical Center, Brooklyn, NY, USA
    J Lipid Res 53:901-8. 2012
    ..In this mechanism, NR2F1 does not affect activities of individual transcription factors; instead, it abrogates synergistic activation by HNF-4α and HNF-1 proteins...
  15. ncbi Association testing of variants in the hepatocyte nuclear factor 4alpha gene with risk of type 2 diabetes in 7,883 people
    Wendy Winckler
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetes 54:886-92. 2005
    ..reported association of common polymorphisms in the P2 promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with risk for type 2 diabetes...
  16. doi The stable repression of mesenchymal program is required for hepatocyte identity: a novel role for hepatocyte nuclear factor 4α
    Laura Santangelo
    Department of Cellular Biotechnologies and Hematology, Pasteur Institute Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy
    Hepatology 53:2063-74. 2011
    ..Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by ..
  17. ncbi Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type 2 diabetes in the Japanese population
    Kazuo Hara
    Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Diabetes 55:1260-4. 2006
    ..type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene is located...
  18. pmc Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer
    Karthikeyani Chellappa
    Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA
    Proc Natl Acad Sci U S A 109:2302-7. 2012
    ..The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) has just recently been implicated in colon cancer but its role is poorly defined...
  19. doi Identification of HNF1A-MODY and HNF4A-MODY in Irish families: phenotypic characteristics and therapeutic implications
    M P Kyithar
    Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland
    Diabetes Metab 37:512-9. 2011
    The prevalence of hepatocyte nuclear factor (HNF)-1A and HNF4A mutations, and the clinical implications following the genetic diagnosis of maturity-onset diabetes of the young (MODY) in the Irish population, remain unknown...
  20. pmc SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4
    J C Wang
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 273:30847-50. 1998
    Hepatocyte nuclear factor-4 (HNF4), a member of the nuclear receptor superfamily, plays an important role in tissue-specific gene expression, including genes involved in hepatic glucose metabolism...
  21. pmc Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations
    S E Flanagan
    Peninsula Medical School, Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK
    Eur J Endocrinol 162:987-92. 2010
    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)...
  22. ncbi CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression
    H Dell
    Department of Medicine, Section of Molecular Genetics, Cardiovascular Institute, Boston University School of Medicine, Center for Advanced Biomedical Research, Boston, Massachusetts 02118 2394, USA
    J Biol Chem 274:9013-21. 1999
    ..These findings demonstrate that CBP acts as a transcriptional coactivator for HNF-4 and provide new insights into the regulatory function of HNF-4...
  23. ncbi Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes
    Kaisa Silander
    Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA
    Diabetes 53:1141-9. 2004
    ..3 kb downstream of the primary beta-cell promoter P2 of hepatocyte nuclear factor-4 alpha (HNF4A). This SNP showed association with diabetes disease status (odds ratio [OR] 1.33, 95% CI 1.06-1.65, P = 0...
  24. doi The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development
    Lorna W Harries
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK
    Diabetes 57:1745-52. 2008
    Mutations in the alternatively spliced HNF4A gene cause maturity-onset diabetes of the young (MODY)...
  25. ncbi AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability
    Yu Holly Hong
    Department of Pathology and the Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Biol Chem 278:27495-501. 2003
    ..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,..
  26. pmc TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4
    Sohail Malik
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA
    Mol Cell Biol 22:5626-37. 2002
    ..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...
  27. pmc Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product
    Peng Lu
    Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536, USA
    J Biol Chem 283:33685-97. 2008
    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 ..
  28. pmc A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers
    Gregory S Yochum
    Vollum Institute and Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 107:145-50. 2010
    ..Each enhancer directly binds members of the TCF/Lef family of transcription factors that, in turn, recruit beta-catenin...
  29. ncbi Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Barrack Road, Exeter, UK
    Diabetes 53:3002-6. 2004
    ..Rare mutations in the HNF4alpha gene cause maturity-onset diabetes of the young...
  30. ncbi 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
    Jakob Ek
    Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 6, NSK1 14, DK 2820 Gentofte, Denmark
    J Clin Endocrinol Metab 90:3054-9. 2005
    b>HNF4A encodes an orphan nuclear receptor that plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion...
  31. ncbi HNF4A genetic variants: role in diabetes
    Latisha Love-Gregory
    Nutritional Sciences, Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Curr Opin Clin Nutr Metab Care 10:397-402. 2007
    Variants in the hepatocyte nuclear factor 4alpha (HNF4A) gene play a role in the development of diabetes mellitus...
  32. pmc 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
    Gaya Thanabalasingham
    Oxford Centre for Diabetes, Endocrinology andMetabolism, University of Oxford, U K
    Diabetes Care 35:1206-12. 2012
    Misdiagnosis of maturity-onset diabetes of the young (MODY) remains widespread, despite the benefits of optimized management...
  33. ncbi A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes
    Jakob Ek
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    Diabetes 55:1869-73. 2006
    Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are ..
  34. ncbi Effect of common polymorphisms in the HNF4alpha promoter on susceptibility to type 2 diabetes in the French Caucasian population
    M Vaxillaire
    CNRS 8090 Institut de Biologie, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019, Lille, France
    Diabetologia 48:440-4. 2005
    ....
  35. ncbi Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17
    A Argyrokastritis
    Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, Greece
    Hum Genet 99:233-6. 1997
    ..hHFN-4 maps to chromosome 20 in a region syntenic with mouse chromosome 2 where the hnf-4 homologue has been assigned...
  36. ncbi Developmentally regulated N-terminal variants of the nuclear receptor hepatocyte nuclear factor 4alpha mediate multiple interactions through coactivator and corepressor-histone deacetylase complexes
    Maria Elena Torres-Padilla
    Unité de Génétique de la Différenciation, FRE 2364 du CNRS, Departement de Biologie du Developpement, Institut Pasteur, 75724 Paris Cedex 15, France
    J Biol Chem 277:44677-87. 2002
    ..Possible physiological consequences of the multiple interactions with these coregulators are discussed...
  37. ncbi 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
    Anna L Gloyn
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medical and Health Sciences, University of Exeter, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 51:2329-33. 2002
    ..20 break point, 20q12, is within the region of one of the known MODY genes, hepatocyte nuclear factor-4alpha (HNF4A)...
  38. doi HNF4 alpha and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy
    Monika Niehof
    Fraunhofer Institute of Toxicology and Experimental Medicine, Center of Molecular Medicine and Medical Biotechnology, Nikolai Fuchs Str 1, 30625 Hannover, Germany
    Diabetes 57:1069-77. 2008
    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...
  39. ncbi Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205
    Yutaka Maeda
    Environmental Toxicology Graduate Program, University of California, Riverside, California 92521, USA
    Mol Endocrinol 16:1502-10. 2002
    ..remains a mystery, as does the mechanism by which orphan receptors such as hepatocyte nuclear factor 4alpha (HNF4alpha) activate transcription...
  40. pmc Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1
    J L Bento
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Genomics 92:226-34. 2008
    ..The most significant SNPs were found in the perigenic regions: HNF4A (hepatocyte nuclear factor 4alpha), SLC12A5 (potassium-chloride cotransporter member 5), CDH22 (cadherin-like 22), ..
  41. doi Hepatocyte nuclear factor-4alpha and bile acids regulate human concentrative nucleoside transporter-1 gene expression
    Kerstin Klein
    Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, Ramistrasse 100, CH 8091 Zurich, Switzerland
    Am J Physiol Gastrointest Liver Physiol 296:G936-47. 2009
    ..Supporting the physiological relevance and species conservation of this effect, ileal Cnt1 mRNA expression was decreased upon bile acid feeding and increased upon bile duct ligation in mice...
  42. pmc Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies
    Sven Pörksen
    Department of Pediatrics, Glostrup Hospital and University of Copenhagen, Copenhagen, Denmark
    BMC Endocr Disord 10:16. 2010
    ..Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.
  43. pmc Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo
    Serkan Kir
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 287:41334-41. 2012
    ..Here, in a series of loss-of-function studies, we show that the nuclear receptors HNF4α and LRH-1 have dual roles in regulating Cyp7a1 in vivo...
  44. doi Can complement factors 5 and 8 and transthyretin be used as biomarkers for MODY 1 (HNF4A-MODY) and MODY 3 (HNF1A-MODY)?
    E Karlsson
    Department of Clinical Sciences Diabetes and Endocrinology, Malmo University Hospital, Lund University, Malmo, Sweden
    Diabet Med 25:788-91. 2008
    ..We therefore set out to determine whether serum concentrations of C5, C8 and TTR can be used as biomarkers for patients with HNF4A-MODY and HNF1A-MODY.
  45. pmc Proteomic analysis of native hepatocyte nuclear factor-4α (HNF4α) isoforms, phosphorylation status, and interactive cofactors
    Kenji Daigo
    Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153 8904, Japan
    J Biol Chem 286:674-86. 2011
    Hepatocyte nuclear factor-4α (HNF4α, NR2A1) is a nuclear receptor that has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver...
  46. ncbi 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
    Takeshi Ozeki
    Laboratory of Drug Metabolism, Division of Pharmacobio dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Pharmacogenetics 13:49-53. 2003
    ..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...
  47. pmc Effects of hepatocyte nuclear factor-4alpha on the regulation of the hepatic acute phase response
    Zhongyan Wang
    Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA
    J Mol Biol 371:323-35. 2007
    ....
  48. ncbi SMAD proteins transactivate the human ApoCIII promoter by interacting physically and functionally with hepatocyte nuclear factor 4
    D Kardassis
    Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, F O R T H, Heraklion GR 71110, Crete, Greece
    J Biol Chem 275:41405-14. 2000
    ....
  49. doi Protein expression of nuclear receptors in human and murine tissues
    So Takegoshi
    Department of Cellular Function, Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    Pathol Int 59:61-72. 2009
    ..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 ..
  50. ncbi SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes
    Takashi Yamamoto
    Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1 1 1 Tennodai, Tsukuba, Ibaraki 305 8575, Japan
    J Biol Chem 279:12027-35. 2004
    ..Our data indicate that SREBP-1 has a novel role as negative regulator of gluconeogenic genes through a cross-talk with HNF-4alpha interference with PGC-1 recruitment...
  51. pmc Modification in oxidative stress, inflammation, and lipoprotein assembly in response to hepatocyte nuclear factor 4alpha knockdown in intestinal epithelial cells
    Valérie Marcil
    Research Institute, McGill University, Campus MGH, C10 148 6, Montreal H3G 1A4, Quebec
    J Biol Chem 285:40448-60. 2010
    ..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 ..
  52. ncbi HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma
    Belén Lucas
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, D 45122 Essen, Germany
    Oncogene 24:6418-31. 2005
    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...
  53. pmc Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4
    Wan Chih Chou
    Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Heraklion GR 71110, Greece
    Mol Biol Cell 14:1279-94. 2003
    ..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...
  54. pmc Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes
    T Drewes
    Institut für Zelbiologie, Universitatsklinikum Essen, Germany
    Mol Cell Biol 16:925-31. 1996
    Hepatocyte nuclear factor 4 (HNF4) was first identified as a DNA binding activity in rat liver nuclear extracts...
  55. ncbi Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4
    S Reddy
    Department of Cell Biology, Parke Davis Research, Ann Arbor, Michigan 48105, USA
    J Biol Chem 274:33050-6. 1999
    ..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 ..
  56. ncbi Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4
    Hisako Hirokane
    Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113 8657, Japan
    J Biol Chem 279:45685-92. 2004
    ..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...
  57. pmc Mapping of HNF4alpha target genes in intestinal epithelial cells
    Mette Boyd
    Department of Cellular and Molecular Medicine, Panum Institute, Building 6, 4, University of Copenhagen, Blegdamsvej 3B 2200 Copenhagen N, Denmark
    BMC Gastroenterol 9:68. 2009
    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...
  58. ncbi Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns
    Lori L Bonnycastle
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 2152, USA
    Diabetes 55:2534-40. 2006
    ..To complement our previous studies of HNF4A, we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals...
  59. ncbi Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription
    Frank J Gonzalez
    Laboratory of Metabolism, National Cancer Institute, National Instituted of Health, Bethesda, Maryland 20892, USA
    Drug Metab Pharmacokinet 23:2-7. 2008
    Hepatocyte nuclear factor 4alpha (HNF4alpha, NR2A1) is required for development of the liver and for controlling the expression of many genes specifically expressed in the liver and associated with a number of critical metabolic pathways...
  60. ncbi Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha
    Elyhisha A Hanniman
    Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
    J Lipid Res 47:2503-14. 2006
    ..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...
  61. pmc The ERK1/2-hepatocyte nuclear factor 4alpha axis regulates human ABCC6 gene expression in hepatocytes
    Hugues de Boussac
    Institute of Enzymology, Hungarian Academy of Sciences, Karolina ut 29, 1113 Budapest, Hungary
    J Biol Chem 285:22800-8. 2010
    ..the tissue-specific expression pattern to the gene and with a putative hepatocyte nuclear factor 4alpha (HNF4alpha) binding site...
  62. ncbi Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha and steroid receptor coactivator 1
    Celia P Martinez-Jimenez
    Unidad de Hepatologia Experimental, Centro de Investigacion, Hospital La Fe, Avenida de Campanar, 21, 46009 Valencia, Spain
    Mol Pharmacol 70:1681-92. 2006
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a key transcription factor for the constitutive expression of cytochromes P450 (P450s) in the liver...
  63. ncbi Hepatocyte nuclear factor-4{alpha} regulates the human organic anion transporter 1 gene in the kidney
    Ken Ogasawara
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan
    Am J Physiol Renal Physiol 292:F1819-26. 2007
    ..This paper reports the first characterization of the human OAT1 promoter and the first gene in the kidney whose promoter activity is regulated by HNF-4alpha...
  64. pmc Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8
    Koichi Sumi
    Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4 6 1 Komaba, Meguro, Tokyo, Japan
    Mol Cell Biol 27:4248-60. 2007
    ..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 ..
  65. pmc Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line
    Heike Thomas
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, D 45122 Essen, Germany
    Nucleic Acids Res 32:e150. 2004
    ..Using a clone expressing the HNF6, HNF4alpha and HNF1beta transcription factors at a limited level, we introduced the expression vectors encoding these ..
  66. doi Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations
    Ritika R Kapoor
    London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children NHS Trust, and the Institute of Child Health, University College London, London, UK
    Diabetes 57:1659-63. 2008
    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-..
  67. ncbi Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor
    Jiandie Lin
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:1645-8. 2002
    ..HCF is shown to bind to both PGC-1alpha and -1beta and augment their transcriptional activity...
  68. pmc Hepatocyte nuclear factor 4alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9
    Hiroto Ohguchi
    Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153 8904, Japan
    Mol Cell Biol 28:3917-31. 2008
    ..Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression...
  69. doi Novel monogenic diabetes mutations in the P2 promoter of the HNF4A gene are associated with impaired function in vitro
    A Wirsing
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, Universitat Duisburg Essen, Germany
    Diabet Med 27:631-5. 2010
    Mutations in HNF4A cause a form of monogenic beta-cell diabetes...
  70. pmc 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
    Yuxia Zhang
    Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
    J Biol Chem 286:29635-43. 2011
    ..Hepatocyte nuclear factor 4α (HNF4α) activated the Egr-1 promoter through three DR1 response elements as identified by trans-activation assays...
  71. pmc Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis
    Sabyasachi Sanyal
    Department of Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital, S 14157 Huddinge, Sweden
    Proc Natl Acad Sci U S A 104:15665-70. 2007
    ..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)...
  72. pmc Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors
    G Jiang
    Environmental Toxicology Graduate Program, University of California, Riverside 92521, USA
    Mol Cell Biol 15:5131-43. 1995
    ..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...
  73. pmc Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A
    Diana E Stanescu
    Clinical and Translational Research Center, The Children s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, 3615 Civic Center Boulevard, Abramson Research Center Room 802A, Philadelphia, Pennsylvania 19104, USA
    J Clin Endocrinol Metab 97:E2026-30. 2012
    Inactivating mutations in HNF1A and HNF4A cause the maturity-onset diabetes of youth (MODY)-3 and MODY1 forms of monogenic diabetes, respectively...
  74. ncbi Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha
    S Pruhova
    Department of Paediatrics, 3rd Faculty of Medicine, Charles University, Vinohradska 159, 100 81 Prague 10, Czech Republic
    Diabetologia 46:291-5. 2003
    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.
  75. pmc The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression
    Y K Lee
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 20:187-95. 2000
    ..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...
  76. pmc Novel polymorphisms of nuclear receptor SHP associated with functional and structural changes
    Taofeng Zhou
    Department of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
    J Biol Chem 285:24871-81. 2010
    ..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...
  77. pmc Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation
    Dipanjan Chanda
    Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea
    Nucleic Acids Res 38:4607-19. 2010
    ....
  78. ncbi Acetylation regulates transcription factor activity at multiple levels
    E Soutoglou
    Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas, Herakleion Crete, Greece
    Mol Cell 5:745-51. 2000
    ..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...
  79. pmc Mitogen-activated protein kinase-mediated disruption of enhancer-promoter communication inhibits hepatocyte nuclear factor 4alpha expression
    Pantelis Hatzis
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Herakleion, Crete, Greece
    Mol Cell Biol 26:7017-29. 2006
    ....
  80. ncbi Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors
    N Masuda
    Department of Life Science, Himeji Institute of Technology, Kamigori, Hyogo 678 1297, Japan
    Gene 221:225-33. 1998
    ..NRBF-1 has a significant homology to the yeast protein MRF1, a putative transcription factor regulating the expression of mitochondrial respiratory proteins. NRBF-1 might be another type of nuclear receptor co-operator...
  81. ncbi Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4
    A A Kritis
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Herakleion, Crete, Greece
    Gene 173:275-80. 1996
    ....
  82. pmc FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol
    Goutham Kumar Ganjam
    Faculty of Chemistry, Department of Biochemistry, University of Kaiserslautern, D 67663 Kaiserslautern, Germany
    J Biol Chem 284:30783-97. 2009
    ..These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol...
  83. ncbi Nitric oxide and TGF-beta1 inhibit HNF-4alpha function in HEPG2 cells
    Susana de Lucas Sd
    Fundacion para el Estudio de las Hepatitis Virales, Madrid, Spain
    Biochem Biophys Res Commun 321:688-94. 2004
    ..TGF-beta1 and nitric oxide inhibit HNF-4alpha activity. These findings may explain the loss of liver functions that occurs during fibrosis progression...
  84. ncbi Differential regulation of constitutive androstane receptor expression by hepatocyte nuclear factor4alpha isoforms
    Jean Marc Pascussi
    INSERM, U632, Montpellier, France
    Hepatology 45:1146-53. 2007
    ..hepatocytes, electromobility shift and cotransfection assays, we identified a functional and species-conserved HNF4alpha response element (DR1: ccAGGCCTtTGCCCTga) at nucleotide -144...
  85. pmc Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential
    E Ktistaki
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Herakleion Crete, Greece
    Proc Natl Acad Sci U S A 92:9876-80. 1995
    ..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...
  86. pmc Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action
    Ines Barroso
    Incyte, Palo Alto, California, USA
    PLoS Biol 1:E20. 2003
    ..2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both ..
  87. doi HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells
    Karen Grigo
    Institut für Zellbiologie Tumorforschung, Universitatsklinikum Essen, Universitat Duisburg Essen, D 45122 Essen, Germany
    Biol Chem 389:179-87. 2008
    ..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 ..
  88. doi Regulation of vascular endothelial growth factor D by orphan receptors hepatocyte nuclear factor-4 alpha and chicken ovalbumin upstream promoter transcription factors 1 and 2
    Georgia Schäfer
    Laboratory for Angiogenesis and Tumor Metastasis, Charite University Hospital, Berlin, Germany
    Cancer Res 68:457-66. 2008
    ..The vegf-D DR element is bound and activated by the orphan receptors hepatocyte nuclear factor 4 alpha (HNF-4 alpha) and chicken ovalbumin upstream promoter transcription factor (COUP-TF)-1/COUP-TF2...
  89. pmc beta-Catenin/TCF/LEF regulate expression of the short form human Cripto-1
    Shin Hamada
    Mammary Biology and Tumorigenesis Laboratory, NCI CCR, 37 Convent Drive, Building 37, Bethesda, MD 20892, USA
    Biochem Biophys Res Commun 355:240-4. 2007
    ..of human colorectal tumors and hepatomas are known to possess a constitutively active canonical Wnt/beta-catenin/TCF signaling pathway, also express CR-1...
  90. ncbi HNF-4alpha: from MODY to late-onset type 2 diabetes
    Rana K Gupta
    Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Blvd, Philadelphia, PA 19104, USA
    Trends Mol Med 10:521-4. 2004
    Maturity-onset diabetes of the young (MODY) is a rare subtype of type 2 diabetes that is characterized by autosomal-dominant inheritance and can be caused by mutations in hepatocyte nuclear factor 4alpha (HNF-4alpha)...
  91. pmc A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene
    Kwang Hoon Song
    Department of Microbiology, Immunology and Biochemistry, Northeastern Ohio University College of Medicine, 4209 State Route 44, Rootstown, OH 44272, USA
    J Biol Chem 281:10081-8. 2006
    ..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-..
  92. ncbi E-cadherin-dependent transcriptional control of apolipoprotein A-IV gene expression in intestinal epithelial cells: a role for the hepatic nuclear factor 4
    Gregory Peignon
    Université Pierre et Marie Curie UMRS 505, Paris, F 75006 France, INSERM, UMRS 505, F 75006 Paris, France
    J Biol Chem 281:3560-8. 2006
    ..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...
  93. ncbi Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes
    Wendy Winckler
    Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Diabetes 56:685-93. 2007
    ..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 ..
  94. ncbi 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
    Yoshiteru Kamiyama
    Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Drug Metab Pharmacokinet 22:287-98. 2007
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is an important transcription factor in hepatic gene expression...
  95. pmc Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
    Ewan R Pearson
    Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 4:e118. 2007
    ..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 ..
  96. ncbi Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha (HNF4A)
    S S Fajans
    Diabetologia 50:2600-1. 2007
  97. ncbi Gene-gene interactions between HNF4A and KCNJ11 in predicting Type 2 diabetes in women
    L Qi
    Department of Nutrition, Harvard Medical School of Public Health, Boston, MA 02115, USA
    Diabet Med 24:1187-91. 2007
    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)...
  98. ncbi P2 promoter variants of the hepatocyte nuclear factor 4alpha gene are associated with type 2 diabetes in Mexican Americans
    Donna M Lehman
    Department of Medicine Clinical Epidemiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
    Diabetes 56:513-7. 2007
    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 ..
  99. pmc Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies
    Ines Barroso
    Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
    Diabetes 57:3161-5. 2008
    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 ..
  100. ncbi 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
    Stefan Johansson
    Department of Clinical Medicine, University of Bergen, Bergen, Norway
    Diabetes 56:3112-7. 2007
    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 ..
  101. pmc DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression
    Balachandar Nedumaran
    Hormone Research Center, School of Biological Science and Technology, Chonnam National University, Gwangju 500 757, South Korea
    J Biol Chem 284:27511-23. 2009
    ..b>HNF4alpha (hepatocyte nuclear factor 4alpha) is a liver-enriched transcription factor that controls the expression of a ..

Research Grants71

  1. Analysis of intestinal genes regulated by the transcription factor CDX2
    Ramesh A Shivdasani; Fiscal Year: 2013
    ..We also find significant co-occupancy of the nuclear receptor HNF4) near CDX2-activated genes and of GATA proteins near genes that CDX2 appears to repress...
  2. REGULATION OF EPIDERMAL DEVELOPMENT AND DIFFERENTIATION
    Elaine Fuchs; Fiscal Year: 2013
    ..2-Catenin acts as a co-factor for the Lef1/Tcf family of DNA binding proteins...
  3. Identifying mechanisms of liver stem cell proliferation and differentiation
    CARL BARTH ROUNTREE; Fiscal Year: 2010
    ..CD133+ oval cells will be defined by bi-lineage potential and stem cell expression profile (Albumin, aFP, Ck19 and Hnf4a). Single cell in-vitro clonal analysis will document bi-potency...
  4. New insights in mechanisms of renal injury
    Balakuntalam S Kasinath; Fiscal Year: 2013
    ..Chromatin immunoprecipitation (ChIP) assays will be performed to study GSK 3beta regulation of binding of Groucho, TCF/LEF1 to the fibronectin promoter...
  5. A Cis-regulatory Model for Neural Border Induction
    Daniel Meulemans Medeiros; Fiscal Year: 2013
    ..Wnt and BMP signals can regulate transcription through activation of their canonical downstream effectors, TCF/LEF and SMAD1/5/8 transcription factors, or through several non- canonical effectors...
  6. Structure-Based Design of Novel HNF4a Antagonists to Treat Metabolic Syndrome
    Arnold T Hagler; Fiscal Year: 2010
    ..this need, we will adopt a novel approach to the problem, designing antagonists that target the nuclear receptor HNF4a. HNF4a is a transcription factor involved in lipid and glucose homeostasis and the transcriptional regulation of ..
  7. BIOLOGY OF SUBMUCOSAL GLAND STEM CELLS IN THE AIRWAY
    John F Engelhardt; Fiscal Year: 2013
    ..models, exvivo xenograft airway models, and genetic mouse models to study how Wnts, Noggin, and BMPs coordinate TCF/Sox regulation of the Lef-1 promoter during submucosal gland morphogenesis...
  8. Role of FoxOs in Skeletal Homeostasis
    MARIA JOSE ALMEIDA; Fiscal Year: 2013
    ..antagonism, whereby activation of FoxO transcription factors diverts the limited pool of 2-catenin from Wnt induced TCF/Lef- transcription to FoxO-mediated transcription was elucidated...
  9. Inhibited Intramembranous Bone Healing in Diabetes
    Philip C Trackman; Fiscal Year: 2013
    ..be tested here is that AGEs and TNF-a each stimulate increased levels of active nuclear FOXO1, which competes with TCF/LEF transcription factors for the available pool of [unreadable]-catenin...
  10. STRESS-RELATED CHANGES IN GENE EXPRESSION AS BIOMARKERS OF RELAPSE VULNERABILITY
    ROBERT DAVID BEECH; Fiscal Year: 2010
    ..Key transcription factors implicated by these gene- expression differences include HNF4-alpha, c-myc, ESR1, AR, and NF-:B...
  11. Notch and Wnt signaling in protection by nandrolone against disuse atrophy
    Christopher Cardozo; Fiscal Year: 2012
    ..analysis of the sequence of the Numb promotor suggests that it contains binding sites for transcription factors (TCF/LEF) by which Wnts regulate gene expression through activation and nuclear translocation of the transcriptional ..
  12. CHARACTERIZATION OF TUMOR SUPPRESSION BY THE APC GENE
    JOANNA LOUISE GRODEN; Fiscal Year: 2010
    ..controlled by GSK3IB phosphorylation and affects the expression of genes regulated by transcription factors of the TCF/LEF family (Clevers and van de Wetering, 1997)...
  13. Integration of RNAi, proteomic and chemical genetic approaches to identify specif
    Ramanuj DasGupta; Fiscal Year: 2009
    ..will be tested for their ability to alter ?-cat's interaction with its known protein partners, such as Tcf, Bcl9/legless (lgs), pygopus (pygo), APC and Axin using FRET and co-immunoprecipitation assays...
  14. Genetics of Obesity in Yup'ik Eskimos
    BERT BRANDON BOYER; Fiscal Year: 2011
    ..regulatory element binding protein (17p11), insulin sensitive glucose transporter (17p13), and hepatocyte nuclear factor 4 alpha (20q12)...
  15. Metabolic and Mitochondrial Defects of Islet beta-cells of MODY-3
    Gary Cline; Fiscal Year: 2009
    ..the impaired glucose stimulated insulin secretion responsible for maturity-onset diabetes of the young type 3 (MODY-3). This research will augment on-going research of the PI into islet beta-cell physiology...
  16. Histone Acetylation and Insulin Gene Expression
    Sabire Ozcan; Fiscal Year: 2010
    ..Several of the diabetes-causing mutations in the MODY genes HNF-1alpha and HNF-4alpha interfere with their interaction with histone acetylases...
  17. Regulation and Function of Drosophila Nuclear Receptors
    Carl S Thummel; Fiscal Year: 2013
    ..found in humans, spanning all vertebrate NR subclasses and encoding homologs of key human receptors, including HNF4 (dHNF4), LXR/FXR (DHR96), LRH-1 (DHR39), NR4A receptors (DHR38), and ERR (dERR)...
  18. Transcriptional control of collective cell migration
    Lionel Christiaen; Fiscal Year: 2013
    ..proteins (BMP) contributes to the L-T polarized expression of downstream target genes, including the Lef/Tcf transcription factor;and (2) these transcriptional inputs determine the L-T polarized activities of the Rho GTPases ..
  19. Molecular Control of Shh-Gli Signaling in the Vertebrate CNS
    Michael P Matise; Fiscal Year: 2010
    ..ventral neuronal progenitor domains involves the transcriptional integration of "canonical" Shh-Gli and Wnt-Tcf signaling elements...
  20. Regulation of Lipid and Lipoprotein Metabolism by Nuclear Receptors
    Yanqiao Zhang; Fiscal Year: 2013
    ..We have very recently shown that activation of FXR i) lowers plasma cholesterol levels likely via a novel FXR-HNF4a-SR-BI pathway, ii) inhibits intestinal cholesterol absorption and iii) increases reverse cholesterol transport, a ..
  21. CATENINS, CADHERINS AND THEIR INTERACTIONS
    William I Weis; Fiscal Year: 2012
    ..5. The molecular mechanism of how Tcf/Lef-family transcription factors control Wnt target signaling will be investigated by determining structures of Lef-..
  22. Regulation of HNF4 in Hepatic Failure in Cirrhosis
    Joseph D Locker; Fiscal Year: 2013
    ..demonstrated that progression to hepatocyte failure was associated with down regulation of transcription factor HNF4[unreadable] and suppression of its regulatory network...
  23. Functional characterization of pathways regulated by schizophrenia gene TCF4
    JOSEPH LOUIE MCCLAY; Fiscal Year: 2013
    ..The time is right to further characterize the function of TCF and the pathways in which it participates, to obtain better insight into schizophrenia pathogenesis...
  24. Molecular Mechanisms of Oligodendrocyte Differentiation and Myelination
    QING R LU; Fiscal Year: 2013
    ..Activation of canonical Wnt signaling by stabilization of the [unreadable]-catenin/TCF complex was shown to inhibit oligodendrocyte differentiation...
  25. A Study of the Cellular Mechanisms Causing Progression to Diabetes in HNF1A-MODY
    Megan R Determan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): HNF1A-MODY is the most prevalent form of monogenic diabetes in humans and results from a haploinsufficiency of the transcription factor hepatocyte nuclear factor 1 alpha (HNF1A)...
  26. RNA-binding protein CRD-BP in melanocyte biology
    Vladimir S Spiegelman; Fiscal Year: 2013
    ..We identified CRD-BP as a novel target of b-catenin/Tcf, and c-myc transcription factors...
  27. TCF3: A Wnt Pathway Effector in Pluripotent Stem Cell Self-Renewal
    Marian L Waterman; Fiscal Year: 2013
    ..about pluripotency through study of the Wnt pathway effectors, T cell factor and Lymphoid enhancer factors (TCF/LEFs)...
  28. Targeted Screen for Novel Chemical Modulators of Wnt/Beta-Cat Signaling Pathway.
    Ramanuj DasGupta; Fiscal Year: 2013
    ..with its known protein interaction partners, or their ability to alter the DNA binding properties of ?-cat/TCF-transcriptional complex using co- immunoprecipitation, immunolocalization, and EMSA assays...
  29. Programming dendritic cells to induce tolerogenic response and suppress brain inf
    Santhakumar Manicassamy; Fiscal Year: 2013
    ..Now, we show that, functionally, the [unreadable]-catenin/TCF signaling pathway plays a critical biological role in programming DCs and Macrophages to induce tolerogenic ..
  30. Transcriptional Regulation of the Intestinal Epithelium
    Michael P Verzi; Fiscal Year: 2013
    ..differentially cooperates with specific transcription factors in progenitor and differentiated cells, GATA6 and HNF4(, respectively...
  31. Genetic modulation of Wingless/Wnt signaling
    AMY M BEJSOVEC; Fiscal Year: 2012
    ..This lab has identified by mutational analysis many important pathway components, such as Tcf, the transcription factor that activates Wnt target genes, and Apc2, a human tumor suppressor homolog that ..
  32. FXR, nuclear receptors, and transcriptional regulation of liver homeostasis
    Grace L Guo; Fiscal Year: 2011
    ..My hypothesis is that ONRs facilitate chromatin modification for subsequent FXR binding and FXR interaction with HNF4&#945;is crucial in orchestrating transcription of target genes critical for liver function...
  33. Characterization of the cleaved carboxy-terminal tail of Polycysin-1
    David M Merrick; Fiscal Year: 2010
    ..Several lines of evidence indicate that PC-1 inhibits cell proliferation through regulation of the Tcf-mediated Wnt signaling pathway...
  34. Hepatocyte Nuclear Factor 4alpha and Lipid Homeostasis
    Yanqiao Zhang; Fiscal Year: 2010
    ..Loss-of-function mutations in human HNF4 are associated with maturity-onset diabetes of the young 1 (MODY1), characterized by autosomal dominant inheritance and early onset diabetes...
  35. Beta-catenin biology in regeneration of uterine smooth muscle
    JOSE M TEIXEIRA; Fiscal Year: 2012
    ..the stabilization of 2-catenin and its translocation to the nucleus and interaction with the transcription factors TCF/LEF to modulate target gene expression...
  36. TRANSCRIPTIONAL CONTROL OF PANCREATIC DEVELOPMENT
    Klaus H Kaestner; Fiscal Year: 2013
    ..in the etiology of diabetes is exemplified by the fact that five of the six known forms of monogenic diabetes (MODY) result from mutations in genes encoding these factors...
  37. LEF/TCF Function in Adult Stem Cell Fate and Tumorigenesis
    Stephen R Lyle; Fiscal Year: 2010
    ..The LEF/TCF family of transcription factors play an essential role in stem cell-mediated skin homeostasis...
  38. Growth Factor Signaling in Intestinal Development
    Steven Cohn; Fiscal Year: 2009
    ..Aim 2 will examine whether the effects of FGFR3 on crypt morphogenesis are mediated through a beta-catenin/TCF-4 dependent mechanism...
  39. Hepatic Lipid Mobilization by Nuclear Hormone Receptors
    Yoon Kwang Lee; Fiscal Year: 2013
    ..split 6 (Hes6) a transcriptional corepressor that has recently been reported to repress PPAR?2 via inhibition of HNF4? transactivation...
  40. Role of ubiquitination in the Wnt pathway
    Ethan Lee; Fiscal Year: 2013
    ..activation results in accumulation of nuclear b-catenin that displaces the co-repressor, Groucho(Gro)/TLE, from the TCF/Lef transcription factor...
  41. LEF/TCF Expression in Colon Cancer
    Marian L Waterman; Fiscal Year: 2012
    ..Wnt signals into changes in target gene expression are members of the Lymphoid Enhancer Factor/T Cell Factor (LEF/TCF) family...
  42. Therapeutic Targeting of Wnt Signaling
    Dianqing Wu; Fiscal Year: 2012
    ..Through a cascade of events, beta-catenin is stabilized and forms a complex with the TCF/LEF-1 transcription factors to activate gene transcription...
  43. HNF4 Isoforms in Physiology and Disease
    Frances M Sladek; Fiscal Year: 2013
    ..well characterized for its role in early development, liver differentiation and an inherited form of diabetes (MODY1)...
  44. G-quadruplex in Translational Regulation and Cancer Therapy
    Hong Lu; Fiscal Year: 2013
    ..Literature reports strongly suggest that restoration of the master regulator HNF4? can treat not only liver cancer, but also liver fibrosis...
  45. Mechanisms Controlling RPE Development
    Sabine Fuhrmann; Fiscal Year: 2013
    ..We will also determine whether Wnt/-catenin through TCF/LEF transcription factors directly activates RPE-specific gene expression using luciferase and ChIP assays (Aim 2)...
  46. Identification of Allsoteric Ligands for Hepatic Nuclear Factor 4-alpha
    Fraydoon Rastinejad; Fiscal Year: 2013
    ..Mutations in HNF4 cause Maturity Onset of Diabetes in Young 1 (MODY1), and hyperinsulinemic hypoglycemia (HH) in humans...
  47. Effects of PGE2 on reconstitution of hematopoiesis and immunity after UCBT
    Corey S Cutler; Fiscal Year: 2013
    ..EP2/EP4 receptors and cAMP-mediated phosphorylation of Gsk3, resulting in stabilization of [unreadable]-catenin and TCF-mediated transcription...
  48. Targeted Therapy for AML Stem Cells
    Kapil Bhalla; Fiscal Year: 2013
    ..causing increased nuclear localization and interaction of [unreadable]-catenin with the bipartite TCF/LEF transcription factor...
  49. Transcriptional Control of Human Placental Differentiation
    Stuart Handwerger; Fiscal Year: 2013
    ..extracellular factors that induce CTB cell differentiation stimulate AP-21 expression that the Wnt-beta-catenin- TCF pathway inhibits AP-21 expression during CTB cell differentiation and that AP-21 expression is abnormal in ..
  50. Osteoblast differentiation: Interactions of Wnt, Runx2 and FGF
    Thomas G Boyer; Fiscal Year: 2012
    ..Moreover, the osteoblast-specific transcription factor, Runx2, binds to the Wnt-dependent transcription factor LEF/TCF and thereby stimulates the FGF18 promoter...
  51. Regulation of Canonical Wnt Signaling by the beta-Catenin Antagonist Chibby
    Feng Qian Li; Fiscal Year: 2010
    ..then translocates into the nucleus where it forms a complex with the T-cell factor/lymphoid enhancer factor (Tcf/Lef) family of transcription factors to stimulate target gene expression...
  52. WNT SIGNALS IN SKIN AND HAIR DEVELOPMENT AND HAIR GROWTH
    Sarah E Millar; Fiscal Year: 2013
    ..cytoplasmic b-catenin allowing it to enter the nucleus and activate transcription in partnership with LEF/TCF transcription factors, and non-canonical pathways that control epithelial planar cell polarity, the actin ..
  53. SNAIL-Dependent Regulation of EMT in Cancer
    STEPHEN JOSEPH WEISS; Fiscal Year: 2010
    ..preliminary data, we now identify a novel regulatory cascade wherein canonical Wnt signaling and the beta- catenin/TCF transcriptional cascade initiate EMT by inducing the Axin2-dependent regulation of GSK3beta nucleo-cytoplasmic ..
  54. A model system to study the tumor suppressor APC and its role in Wnt regulation.
    David Roberts; Fiscal Year: 2013
    ..Together with its nuclear partners (members of the TCF/LEF family), [unreadable]-catenin functions as a bi- partite transcription factor, promoting expression of Wnt ..
  55. MECHANISMS OF BETA CELL FAILURE
    Domenico Accili; Fiscal Year: 2013
    ..or differentiated ?-cells devlop MODY, with striking abnormalities of the transcriptional networks regulated by Hnf4a, Hnf1a, and Pd1...
  56. Mouse Models of Sporadic Colorectal Cancer
    MELINDA ANGUS-HILL; Fiscal Year: 2012
    ..degradation pathway is inhibited, (-catenin accumulates in the cytoplasm and nucleus and binds and transactivates Tcf/Lef proteins. Tcf4 is a member of the Tcf/Lef family of transcription factors...
  57. The effect of Wnt pathway signaling in NSCLC
    Robert Winn; Fiscal Year: 2009
    ..in stabilization and nuclear accumulation of the transcriptional co-activator, b-catenin, which interacts with TCF/LEF transcription factors to activate target genes...
  58. Wnt signaling in Colon Cancer
    Marian L Waterman; Fiscal Year: 2013
    ..The transcription factors that mediate Wnt signals are members of the Lymphoid Enhancer Factor/T Cell Factor (LEF/TCF) family...
  59. Transcriptional Regulation of Mammalian Hepatic Development
    Stephen A Duncan; Fiscal Year: 2013
    ..whether the hepatocyte dysfunction contributes to the pathophysiology of Maturity Onset Diabetes of the Young (MODY)...
  60. Natural helper cells in allergic airway inflammation
    Avinash Bhandoola; Fiscal Year: 2013
    ..similar gene expression profile as T cell lineage progenitors, and that the development of NH cells is dependent on TCF-1, an essential transcription factor in early T cell development...
  61. Virus/host interaction in HIV neuropathogenesis
    LISA JANE HENDERSON; Fiscal Year: 2012
    ..HIV replication, partially as a result of removal of the downstream effector of the Wnt/Beta-catenin pathway, TCF-4, from the HIV LTR...
  62. Function of 9-cis-retinoic acid
    Joseph L Napoli; Fiscal Year: 2013
    ..e. defects in Pdx-1 and HNF41 underlie MODY4 and MODY1, respectively. A defect in the gene that encodes glucokinase underlies a third MODY, i.e...
  63. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2010
    ..The roles of HNF4? and FTP, and their co-regulators Prox1, PGC-1?, histone deacetylase (HDAC) and silencing information regulator (..
  64. Geographically robust rapid assay for T. cruzi infection
    SYAMAL X RAYCHAUDHURI; Fiscal Year: 2010
    ..2. The ITC8.2 has been used extensively in rapid assay formats (Trypanosoma DetectTM). This recombinant contains TcF (currently used in Abbott assay and contains four different repeating epitopes) fused with five additional peptide ..
  65. ENDOCRINE PANCREAS: GENE EXPRESSION AND REGULATION
    Doris Stoffers; Fiscal Year: 2000
    ..In particular, recent advances elucidating the genetic basis of a subset of diabetes, MODY (maturity onset diabetes of the young), have indicated links among pancreatic transcription factors, beta-cell ..
  66. HYPERTENSION IN AFRICAN-AMERICAN WOMEN
    Ashok Kumar; Fiscal Year: 2004
    ..The human AG gene is primarily expressed in the liver and we have shown that liver enriched transcription factors HNF4 and DBP, and ubiquitous transcription factors SP1 and CREB play important role in liver specific expression of this ..
  67. The Role of Beta-catenin/Tcf Pathway Defects in Cancer
    Eric Fearon; Fiscal Year: 2009
    ..or cancer-related mutations leads to beta-catenin nuclear accumulation and its enhanced binding to T cell factor (TCF) family of transcription factors...
  68. Hhex-a Homeobox Gene Necessary for Liver Development
    Clifford W Bogue; Fiscal Year: 2010
    ..Furthermore, we showed that deletion of Hhex is associated with decreased expression of Hnf4a, Hnf1b (TCF2) and Onecut1 (Hnf6), suggesting that Hhex regulates, either directly or indirectly, the expression of ..
  69. Host signaling factors that repress HIV replication
    Lena Al Harthi; Fiscal Year: 2009
    ..of Wnt/2-catenin signaling by transfection of dominant negative mutant constructs to either T cell factor-4 (TCF-4), the down-stream effector of Wnt signaling, or ?-catenin, the central mediator of this pathway, (i) abrogated ..
  70. PDK1 and PPARdelta Signaling in Mammary Tumorigenesis
    Robert I Glazer; Fiscal Year: 2010
    ..hypothesis that 3-phosph6inbsitide-dependent protein kinase-1 (PDK1) activates and interacts with the ff-eaten in/TCF-target gene, peroxisome proliferator-activated receptor-delta (PPARtf). to promote mammary tumorigenesis...
  71. TRANSCRIPTIONAL ACTIVATION BY TRANSCRIPTION COFACTOR-1
    PAUL KHAVARI; Fiscal Year: 1992
    ..We have named this protein transcription cofactor 1 (TCF-1), since it is to our knowledge the first transcriptional cofactor to be identified...