hepatocyte nuclear factor 3 beta


Summary: A forkhead transcription factor that regulates expression of metabolic GENES and is involved in EMBRYONIC DEVELOPMENT. Mutations in HNF-3beta have been associated with CONGENITAL HYPERINSULINISM.

Top Publications

  1. Wallerman O, Motallebipour M, Enroth S, Patra K, Bysani M, Komorowski J, et al. Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37:7498-508 pubmed publisher
    ..An interaction between HNF4a and GABP was seen at TSS, with one-third of the HNF4a positive promoters being bound also by GABP, and this interaction was verified by co-immunoprecipitations. ..
  2. Yu X, Wang Y, Jiang M, Bierie B, Roy Burman P, Shen M, et al. Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration. Prostate. 2009;69:249-62 pubmed publisher
  3. Silva J, von Meyenn F, Howell J, Thorens B, Wolfrum C, Stoffel M. Regulation of adaptive behaviour during fasting by hypothalamic Foxa2. Nature. 2009;462:646-50 pubmed publisher
    ..Our results demonstrate that Foxa2 can act as a metabolic sensor in neurons of the lateral hypothalamic area to integrate metabolic signals, adaptive behaviour and physiological responses. ..
  4. Pandey A, Bhardwaj V, Datta M. Tumour necrosis factor-alpha attenuates insulin action on phosphoenolpyruvate carboxykinase gene expression and gluconeogenesis by altering the cellular localization of Foxa2 in HepG2 cells. FEBS J. 2009;276:3757-69 pubmed publisher
    ..Our results indicate that another transcription factor, Foxa2, is at least partly responsible for the attenuating effect of TNFalpha on insulin action on PEPCK expression and glucose production in HepG2 cells. ..
  5. McKnight K, Hou J, Hoodless P. Foxh1 and Foxa2 are not required for formation of the midgut and hindgut definitive endoderm. Dev Biol. 2010;337:471-81 pubmed publisher
    ..This finding represents a significant insight into specification and regionalization of mouse definitive endoderm. ..
  6. Lamba V, Panetta J, Strom S, Schuetz E. Genetic predictors of interindividual variability in hepatic CYP3A4 expression. J Pharmacol Exp Ther. 2010;332:1088-99 pubmed publisher
    ..This approach identified sex and polymorphisms in FoxA2, HNF4alpha, FoxA3, PXR, ABCB1, and the CYP3A4 promoter that together explained as much as 24.6% of the variation in hepatic CYP3A4 expression. ..
  7. Lin W, Metzakopian E, Mavromatakis Y, Gao N, Balaskas N, Sasaki H, et al. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev Biol. 2009;333:386-96 pubmed publisher
    ..Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes. ..
  8. Zhang Y, Ali T, Zhou H, D Souza D, Lu Y, Jaffe J, et al. ErbB3 binding protein 1 represses metastasis-promoting gene anterior gradient protein 2 in prostate cancer. Cancer Res. 2010;70:240-8 pubmed publisher
    ..Collectively, our results reveal an EBP1-Foxa-AGR2 signaling circuit with functional significance in metastatic prostate cancer. ..
  9. Lehner F, Kulik U, Klempnauer J, Borlak J. Mapping of liver-enriched transcription factors in the human intestine. World J Gastroenterol. 2010;16:3919-27 pubmed
    ..We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut. ..

More Information


  1. Long Y, Chen E, Liu C, Huang F, Zhou T, He F, et al. The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patients. J Viral Hepat. 2009;16:537-46 pubmed publisher
    ..This suggests that HNF4alpha and HNF3beta likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4alpha and HNF3beta in the liver. ..
  2. Chung S, Leung A, Han B, Chang M, Moon J, Kim C, et al. Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell. 2009;5:646-58 pubmed publisher
    ..Together with previous works, this study shows that two regulatory loops (Wnt1-Lmx1a and SHH-FoxA2) critically link extrinsic signals to cell-intrinsic factors and cooperatively regulate mDA neuron development. ..
  3. Nelander J, Hebsgaard J, Parmar M. Organization of the human embryonic ventral mesencephalon. Gene Expr Patterns. 2009;9:555-61 pubmed publisher
    ..This data therefore suggest similar roles for these factors also in human VM development and dopamine neurogenesis. ..
  4. Field Corbett C, English K, O Dea S. Regulation of surfactant protein B gene expression in bone marrow-derived cells. Stem Cells. 2009;27:662-9 pubmed publisher
    ..Furthermore, silencing events, such as methylation, may occur to suppress lung-related gene expression as progenitor cells become committed toward more mature hematopoietic cell phenotypes. ..
  5. Motallebipour M, Ameur A, Reddy Bysani M, Patra K, Wallerman O, Mangion J, et al. Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq. Genome Biol. 2009;10:R129 pubmed publisher
    ..We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation. ..
  6. Qi J, Nakayama K, Cardiff R, Borowsky A, Kaul K, Williams R, et al. Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors. Cancer Cell. 2010;18:23-38 pubmed publisher
    ..Tissue-specific expression of FoxA2 combined with Siah2-dependent HIF-1alpha availability enables a transcriptional program required for NE prostate tumor development and NE phenotype in PCa. ..
  7. Turner J, Jones C. Regulation of mucin expression in respiratory diseases. Biochem Soc Trans. 2009;37:877-81 pubmed publisher
    ..An understanding of the origin and processes regulating goblet cell formation in human airway epithelial cells has important implications for the identification of therapeutic targets to treat respiratory diseases. ..
  8. Arufe M, Lu M, Lin R. Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1. Biochem Biophys Res Commun. 2009;381:264-70 pubmed publisher
    ..Our method provides a powerful in vitro differentiation model for studying the mechanisms of early thyrocyte lineage development. ..
  9. Howell J, Stoffel M. Nuclear export-independent inhibition of Foxa2 by insulin. J Biol Chem. 2009;284:24816-24 pubmed publisher
  10. Gadue P, Gouon Evans V, Cheng X, Wandzioch E, Zaret K, Grompe M, et al. Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm. Stem Cells. 2009;27:2103-13 pubmed publisher
  11. Nock A, Ascano J, Jones T, Barrero M, Sugiyama N, Tomita M, et al. Identification of DNA-dependent protein kinase as a cofactor for the forkhead transcription factor FoxA2. J Biol Chem. 2009;284:19915-26 pubmed publisher
    ..We therefore conclude that DNA-PK-dependent phosphorylation of FoxA2 plays a critical role in its transcriptional activation function per se. ..
  12. Espina A, Méndez Vidal C, Moreno Mateos M, Saez C, Romero Franco A, Japon M, et al. Induction of Dlk1 by PTTG1 inhibits adipocyte differentiation and correlates with malignant transformation. Mol Biol Cell. 2009;20:3353-62 pubmed publisher
  13. Jablonska O, Shi Z, Valdez K, Ting A, Petroff B. Temporal and anatomical sensitivities to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin leading to premature acyclicity with age in rats. Int J Androl. 2010;33:405-12 pubmed publisher
    ..This study reveals a particular sensitivity of the developing ovary to TCDD leading to early loss of reproductive function with age. ..
  14. Song Y, Washington M, Crawford H. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res. 2010;70:2115-25 pubmed publisher
    ..We conclude that suppression of FOXA1/2 expression is both necessary and sufficient for EMT during PDA malignant progression. ..
  15. Huang G, Eisenberg R, Yan M, Monti S, Lawrence E, Fu P, et al. 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer. Cancer Res. 2008;68:5040-8 pubmed publisher
    ..In summary, we identify 15-PGDH as a direct downstream effector of HNF3beta and show that 15-PGDH acts as a tumor suppressor in lung cancer. ..
  16. Jeong J, Kwak I, Lee K, Kim T, Large M, Stewart C, et al. Foxa2 is essential for mouse endometrial gland development and fertility. Biol Reprod. 2010;83:396-403 pubmed publisher
    ..This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse. ..
  17. Popovic J, Klajn A, Petrovic I, Stevanovic M. Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression. Biochim Biophys Acta. 2010;1799:411-8 pubmed publisher
    ..Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression. ..
  18. Rojas A, Schachterle W, Xu S, Martin F, Black B. Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer. Dev Biol. 2010;346:346-55 pubmed publisher
    ..These studies identify Gata4 as a direct transcriptional target of FoxA2 in the hierarchy of the transcriptional regulatory network that controls the development of the definitive endoderm. ..
  19. Strazzabosco M. Foxa1 and Foxa2 regulate bile duct development in mice. J Hepatol. 2010;52:765-7 pubmed publisher
  20. Ye D, Kaestner K. Foxa1 and Foxa2 control the differentiation of goblet and enteroendocrine L- and D-cells in mice. Gastroenterology. 2009;137:2052-62 pubmed publisher
    ..The winged helix factors Foxa1 and Foxa2 are essential members of the transcription factor network that govern secretory cell differentiation in the mammalian gastrointestinal tract. ..
  21. Martinez M, Smith A, Li B, Zhang M, Harrod K. Computational prediction of novel components of lung transcriptional networks. Bioinformatics. 2007;23:21-9 pubmed
    ..DME: http://rulai.cshl.edu/dme. MATCOMPARE: http://rulai.cshl.edu/MatCompare. MOTIFCLASS is available from the authors. ..
  22. Lim S, Pereira L, Wong M, Hirst C, Van Vranken B, Pick M, et al. Enforced expression of Mixl1 during mouse ES cell differentiation suppresses hematopoietic mesoderm and promotes endoderm formation. Stem Cells. 2009;27:363-74 pubmed publisher
    ..Taken together, these studies suggest that high levels of Mixl1 preferentially allocate cells to the endoderm during ESC differentiation. ..
  23. Park J, Tschumperlin D. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am J Respir Cell Mol Biol. 2009;41:459-66 pubmed publisher
    ..We propose that the mechanical environment present in asthma may fundamentally bias the composition of airway epithelial lining in favor of mucin secretory cells. ..
  24. Sekiya T, Muthurajan U, Luger K, Tulin A, Zaret K. Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes Dev. 2009;23:804-9 pubmed publisher
    ..FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin. ..
  25. Bochkis I, Schug J, Rubins N, Chopra A, O Malley B, Kaestner K. Foxa2-dependent hepatic gene regulatory networks depend on physiological state. Physiol Genomics. 2009;38:186-95 pubmed publisher
    ..We show that Foxa2 interacts with different transcription factors to achieve gene expression responses appropriate for each physiologic state. ..
  26. Katoh M, Katoh M. Integrative genomic analyses of CXCR4: transcriptional regulation of CXCR4 based on TGFbeta, Nodal, Activin signaling and POU5F1, FOXA2, FOXC2, FOXH1, SOX17, and GFI1 transcription factors. Int J Oncol. 2010;36:415-20 pubmed
  27. Takasugi M, Yagi S, Hirabayashi K, Shiota K. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions. BMC Genomics. 2010;11:481 pubmed publisher
    ..A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions. ..
  28. Hoffman B, Robertson G, Zavaglia B, Beach M, Cullum R, Lee S, et al. Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver. Genome Res. 2010;20:1037-51 pubmed publisher
    ..Finally, we apply these approaches to generate novel insights into how FOXA2, PDX1, and HNF4A cooperate to drive islet- and liver-specific gene expression. ..
  29. Gao N, Le Lay J, Qin W, Doliba N, Schug J, Fox A, et al. Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell. Mol Endocrinol. 2010;24:1594-604 pubmed publisher
    ..These data demonstrate that Foxa1 and Foxa2 play crucial roles in the development and maintenance of beta-cell-specific secretory and metabolic pathways. ..
  30. Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, et al. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010;184:6133-41 pubmed publisher
    ..The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2. ..
  31. Dayoub R, Groitl P, Dobner T, Bosserhoff A, Schlitt H, Weiss T. Foxa2 (HNF-3beta) regulates expression of hepatotrophic factor ALR in liver cells. Biochem Biophys Res Commun. 2010;395:465-70 pubmed publisher
    ..In addition, we could not detect any binding of C/EBPbeta and IL-6 RE-BP to the promoter of ALR. In conclusion, these results indicate that ALR is regulated by Foxa2, and this regulation may be amplified by IL-6. ..
  32. Tosi J, Janisch K, Wang N, Kasanuki J, Flynn J, Lin C, et al. Cellular and molecular origin of circumpapillary dysgenesis of the pigment epithelium. Ophthalmology. 2009;116:971-80 pubmed publisher
    ..The author(s) have no proprietary or commercial interest in any materials discussed in this article. ..
  33. Li Z, White P, Tuteja G, Rubins N, Sackett S, Kaestner K. Foxa1 and Foxa2 regulate bile duct development in mice. J Clin Invest. 2009;119:1537-45 pubmed publisher
    ..Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression. ..
  34. Lee H, Bae E, Yi S, Shim J, Jo A, Kang J, et al. Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival. Stem Cells. 2010;28:501-12 pubmed publisher
    ..Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD. ..
  35. Freitas H, Schaan B, David Silva A, Sabino Silva R, Okamoto M, Alves Wagner A, et al. SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. Mol Cell Endocrinol. 2009;305:63-70 pubmed publisher
    ..Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. ..
  36. Lazo de la Vega Monroy M, Fernandez Mejia C. [Transcription factors in the adult beta cell]. Rev Invest Clin. 2009;61:428-46 pubmed
    ..The study of transcription factors is crucial for understanding the normal function of the beta cell, essential knowledge in developing new strategies for fighting diabetes. ..
  37. Tuteja G, White P, Schug J, Kaestner K. Extracting transcription factor targets from ChIP-Seq data. Nucleic Acids Res. 2009;37:e113 pubmed publisher
    ..We also use GLITR to address the issue of sequencing depth, and show that sequencing biological replicates identifies far more binding regions than re-sequencing the same sample. ..
  38. Banerjee A, Meyer K, Mazumdar B, Ray R, Ray R. Hepatitis C virus differentially modulates activation of forkhead transcription factors and insulin-induced metabolic gene expression. J Virol. 2010;84:5936-46 pubmed publisher
  39. Fasano C, Chambers S, Lee G, Tomishima M, Studer L. Efficient derivation of functional floor plate tissue from human embryonic stem cells. Cell Stem Cell. 2010;6:336-47 pubmed publisher
    ..These data define the early signals that drive human FP versus AN specification and determine regional identity in hESC-derived FP. ..
  40. Yang H, Nie Y, Li Y, Wan Y. Histone modification-mediated CYP2E1 gene expression and apoptosis of HepG2 cells. Exp Biol Med (Maywood). 2010;235:32-9 pubmed publisher
    ..These results suggest that histone modification is involved in CYP2E1 gene expression and that CYP2E1-dependent mitochondrial oxidative stress plays a role in TSA-induced apoptosis. ..
  41. Nakatani T, Kumai M, Mizuhara E, Minaki Y, Ono Y. Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Dev Biol. 2010;339:101-13 pubmed publisher
  42. Kaestner K. The FoxA factors in organogenesis and differentiation. Curr Opin Genet Dev. 2010;20:527-32 pubmed publisher
  43. Evans N, Minelli C, Gentleman E, LaPointe V, Patankar S, Kallivretaki M, et al. Substrate stiffness affects early differentiation events in embryonic stem cells. Eur Cell Mater. 2009;18:1-13; discussion 13-4 pubmed
  44. Ang S. Foxa1 and Foxa2 transcription factors regulate differentiation of midbrain dopaminergic neurons. Adv Exp Med Biol. 2009;651:58-65 pubmed
  45. Xu H, He J, Xiao Z, Zhang Q, Chen Y, Zhou H, et al. Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology. 2010;52:1431-42 pubmed publisher
    ..Our study provides a model in which miR-122 functions as an effector of LETFs and contributes to liver development by regulating the balance between proliferation and differentiation of hepatocytes, at least by targeting CUTL1. ..
  46. Xing C, Cohen J, Boerwinkle E. A weighted false discovery rate control procedure reveals alleles at FOXA2 that influence fasting glucose levels. Am J Hum Genet. 2010;86:440-6 pubmed publisher
    ..31 mg/dl per minor allele (p value = 2.2 x 10(-11)). This study reveals that there is a cache of less-frequent variants in GWAS arrays that can be identified via analytical approaches accounting for allele frequencies. ..
  47. Park S, Verhaeghe C, Nguyenvu L, Barbeau R, Eisley C, Nakagami Y, et al. Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma. Am J Respir Crit Care Med. 2009;180:603-10 pubmed publisher
    ..Unlike FOXA2, FOXA3 did not regulate mucous metaplasia. ..
  48. Rowbotham N, Hager Theodorides A, Furmanski A, Ross S, Outram S, Dessens J, et al. Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism. Blood. 2009;113:5144-56 pubmed publisher
    ..Gene expression profiling showed that physiologic Hh signaling in thymocytes maintains expression of the transcription factor FoxA2 on pre-TCR signal transduction. ..
  49. Su N, Thiaville M, Awad K, Gjymishka A, Brant J, Yang T, et al. Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor-4-independent pathway. Hepatology. 2009;50:282-90 pubmed publisher
    ..Collectively, the results document that the hepatic FOXA family of genes are differentially regulated by amino acid availability. ..