Gene Symbol: Hnf4a
Description: hepatic nuclear factor 4, alpha
Alias: HNF-4, Hnf4, Hnf4alpha, MODY1, Nr2a1, TCF-14, Tcf14, hepatocyte nuclear factor 4-alpha, HNF4 alpha, Nuclear receptor 2A1, nuclear receptor subfamily 2 group A member 1, transcription factor 14, transcription factor HNF-4
Species: mouse
Products:     Hnf4a

Top Publications

  1. Morrisey E, Tang Z, Sigrist K, Lu M, Jiang F, Ip H, et al. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev. 1998;12:3579-90 pubmed
    ..endoderm and severely attenuate, or fail to express, genes encoding early and late endodermal markers, including HNF4, GATA4, alpha-fetoprotein (AFP), and HNF3beta. Homozygous GATA6(-/-) mice died between embryonic day (E) 6.5 and E7...
  2. Oikawa T, Kamiya A, Kakinuma S, Zeniya M, Nishinakamura R, Tajiri H, et al. Sall4 regulates cell fate decision in fetal hepatic stem/progenitor cells. Gastroenterology. 2009;136:1000-11 pubmed publisher
    ..These results suggest that Sall4 plays a crucial role in controlling the lineage commitment of hepatoblasts not only inhibiting their differentiation into hepatocytes but also driving their differentiation toward cholangiocytes. ..
  3. Tanaka M, Okabe M, Suzuki K, Kamiya Y, Tsukahara Y, Saito S, et al. Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: drastic change of EpCAM expression during liver development. Mech Dev. 2009;126:665-76 pubmed publisher
    ..5 liver contain extrahepatic bile duct cells as well as hepatoblasts, while EpCAM(-)DLK1(+) cells contain mesothelial cell precursors. Thus, the expression of EpCAM and DLK1 suggests the developmental pathways of mouse liver progenitors. ..
  4. Antoniou A, Raynaud P, Cordi S, Zong Y, Tronche F, Stanger B, et al. Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology. 2009;136:2325-33 pubmed publisher
    ..In the embryo, hepatoblasts differentiate to cholangiocytes, which give rise to the bile ducts. Here, we investigated duct development in mouse liver and characterized the role of the SRY-related HMG box transcription factor 9 (SOX9)...
  5. Bonzo J, Ferry C, Matsubara T, Kim J, Gonzalez F. Suppression of hepatocyte proliferation by hepatocyte nuclear factor 4? in adult mice. J Biol Chem. 2012;287:7345-56 pubmed publisher
    ..The hepatocyte-specific Hnf4a knock-out mouse develops severe hepatomegaly and steatosis resulting in premature death, thereby limiting studies ..
  6. Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2011;43:34-41 pubmed publisher
    ..These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status. ..
  7. Hofmann J, Zovein A, Koh H, Radtke F, Weinmaster G, Iruela Arispe M. Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development. 2010;137:4061-72 pubmed publisher
    ..These findings uncover the cellular basis for the defining feature of AGS, identify mesenchymal Jag1-dependent and -independent stages of duct development, and provide mechanistic information for the role of Jag1 in IHBD formation...
  8. Inoue Y, Peters L, Yim S, Inoue J, Gonzalez F. Role of hepatocyte nuclear factor 4alpha in control of blood coagulation factor gene expression. J Mol Med (Berl). 2006;84:334-44 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) plays an important role in the maintenance of many liver-specific functions...
  9. Vincent S, Robertson E. Targeted insertion of an IRES Cre into the Hnf4alpha locus: Cre-mediated recombination in the liver, kidney, and gut epithelium. Genesis. 2004;39:206-11 pubmed
    The Hnf4alpha gene belongs to a family of trancriptional regulators required for liver development and function...

More Information


  1. Parviz F, Matullo C, Garrison W, Savatski L, Adamson J, Ning G, et al. Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet. 2003;34:292-6 pubmed
    ..Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen ..
  2. Hayhurst G, Strick Marchand H, Mulet C, Richard A, Morosan S, Kremsdorf D, et al. Morphogenetic competence of HNF4 alpha-deficient mouse hepatic cells. J Hepatol. 2008;49:384-95 pubmed publisher
    ..specify roles of HNF 4 alpha in mouse liver development, we have analyzed the ex vivo morphogenetic potential of HNF4 alpha-null embryonic hepatic cells...
  3. Babeu J, Darsigny M, Lussier C, Boudreau F. Hepatocyte nuclear factor 4alpha contributes to an intestinal epithelial phenotype in vitro and plays a partial role in mouse intestinal epithelium differentiation. Am J Physiol Gastrointest Liver Physiol. 2009;297:G124-34 pubmed publisher
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a regulator of hepatocyte and pancreatic transcription. Hnf4alpha deletion in the mouse is embryonically lethal with severe defects in visceral endoderm formation...
  4. Li J, Ning G, Duncan S. Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev. 2000;14:464-74 pubmed
    ..We therefore conclude that HNF-4alpha is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function. ..
  5. Garrison W, Battle M, Yang C, Kaestner K, Sladek F, Duncan S. Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon. Gastroenterology. 2006;130:1207-20 pubmed
    b>Hepatocyte nuclear factor 4 alpha (HNF4alpha) is a transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver...
  6. Safdar H, Cheung K, Vos H, Gonzalez F, Reitsma P, Inoue Y, et al. Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4? and C/EBP?. PLoS ONE. 2012;7:e38104 pubmed publisher
    Hepatocyte nuclear factor 4? (HNF4?) and CCAAT/enhancer-binding protein ? (C/EBP?) are important for the transcriptional control of coagulation factors...
  7. Takahashi H, Martin Brown S, Washburn M, Florens L, Conaway J, Conaway R. Proteomics reveals a physical and functional link between hepatocyte nuclear factor 4alpha and transcription factor IID. J Biol Chem. 2009;284:32405-12 pubmed publisher
    ..of a physical and functional link between the orphan nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) and transcription factor IID (TFIID)...
  8. Battle M, Konopka G, Parviz F, Gaggl A, Yang C, Sladek F, et al. Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci U S A. 2006;103:8419-24 pubmed
    ..Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4alpha (HNF4alpha) blocks the epithelial transformation of the fetal liver, suggesting that HNF4alpha is a central regulator of ..
  9. 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. ..
  10. Rhee J, Inoue Y, Yoon J, Puigserver P, Fan M, Gonzalez F, et al. Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci U S A. 2003;100:4012-7 pubmed
    ..known to bind gluconeogenic promoters including the glucocorticoid receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), and the peroxisome proliferator-activated receptors...
  11. Gupta R, Gao N, Gorski R, White P, Hardy O, Rafiq K, et al. Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha. Genes Dev. 2007;21:756-69 pubmed
    ..hepatocyte nuclear factor-4alpha (HNF-4alpha), the gene that is mutated in Maturity-Onset Diabetes of the Young 1 (MODY1)...
  12. Chiba H, Itoh T, Satohisa S, Sakai N, Noguchi H, Osanai M, et al. Activation of p21CIP1/WAF1 gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4alpha. Exp Cell Res. 2005;302:11-21 pubmed
  13. Chen W, Manova K, Weinstein D, Duncan S, Plump A, Prezioso V, et al. Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev. 1994;8:2466-77 pubmed
    ..Development of embryonic structures is severely impaired. These results demonstrate that the expression of HNF-4 in the visceral endoderm is essential for embryonic ectoderm survival and normal gastrulation. ..
  14. Ponugoti B, Fang S, Kemper J. Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c. Mol Endocrinol. 2007;21:2698-712 pubmed
    ..This mechanism may be relevant to known repression of many other HNF-4 target genes upon feeding. ..
  15. Kwon G, Viotti M, Hadjantonakis A. The endoderm of the mouse embryo arises by dynamic widespread intercalation of embryonic and extraembryonic lineages. Dev Cell. 2008;15:509-20 pubmed publisher
  16. Ruland J, Sirard C, Elia A, MacPherson D, Wakeham A, Li L, et al. p53 accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101. Proc Natl Acad Sci U S A. 2001;98:1859-64 pubmed
    ..5. These results demonstrate that tsg101 is essential for the proliferative burst before the onset of gastrulation and establish a functional connection between tsg101 and the p53 pathway in vivo. ..
  17. Walesky C, Edwards G, Borude P, Gunewardena S, O Neil M, Yoo B, et al. Hepatocyte nuclear factor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular carcinoma in rodents. Hepatology. 2013;57:2480-90 pubmed publisher
    b>Hepatocyte nuclear factor 4 alpha (HNF4?), the master regulator of hepatocyte differentiation, has been recently shown to inhibit hepatocyte proliferation by way of unknown mechanisms...
  18. Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez F, Talianidis I. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006;20:2293-305 pubmed
    ..The results illustrate the remarkable flexibility of a self-sustaining transcription factor network, built up by complex dominant and redundant regulatory motifs in developing hepatocytes. ..
  19. 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
    ..these tissues, we globally identify binding sites for FOXA2 in adult mouse islets and liver, PDX1 in islets, and HNF4A in liver...
  20. Rhee J, Ge H, Yang W, Fan M, Handschin C, Cooper M, et al. Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism. J Biol Chem. 2006;281:14683-90 pubmed
    ..In the fasted liver, PGC-1alpha is induced and interacts with hepatocyte nuclear factor 4alpha (HNF4alpha) and other transcription factors to activate gluconeogenesis and increase hepatic glucose output...
  21. Dongol B, Shah Y, Kim I, Gonzalez F, Hunt M. The acyl-CoA thioesterase I is regulated by PPARalpha and HNF4alpha via a distal response element in the promoter. J Lipid Res. 2007;48:1781-91 pubmed
    ..Wy-14,643 and that Acot1 mRNA was also increased by 15-fold in the liver of hepatocyte nuclear factor 4alpha (HNF4alpha) knockout animals...
  22. Kuo C, Morrisey E, Anandappa R, Sigrist K, Lu M, Parmacek M, et al. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 1997;11:1048-60 pubmed
    ..However, they define a critical role for GATA4 in regulating the rostral-to-caudal and lateral-to-ventral folding of the embryo that is needed for normal cardiac morphogenesis. ..
  23. Sirard C, de la Pompa J, Elia A, Itie A, Mirtsos C, Cheung A, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev. 1998;12:107-19 pubmed
    ..Rescued embryos show severe anterior truncations, indicating a second important role for Smad4 in anterior patterning during embryogenesis. ..
  24. Hayhurst G, Lee Y, Lambert G, Ward J, Gonzalez F. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 2001;21:1393-403 pubmed
    ..Of these, only HNF4alpha (nuclear receptor 2A1) and HNF1alpha appear to be correlated with the differentiated phenotype of cultured hepatoma cells...
  25. Inoue Y, Yu A, Yim S, Ma X, Krausz K, Inoue J, et al. Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4alpha. J Lipid Res. 2006;47:215-27 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) regulates many genes that are preferentially expressed in liver...
  26. Miura A, Yamagata K, Kakei M, Hatakeyama H, Takahashi N, Fukui K, et al. Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells. J Biol Chem. 2006;281:5246-57 pubmed
    Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells...
  27. Gupta R, Vatamaniuk M, Lee C, Flaschen R, Fulmer J, Matschinsky F, et al. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J Clin Invest. 2005;115:1006-15 pubmed
    ..Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel. ..
  28. Duncan S, Nagy A, Chan W. Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: tetraploid rescue of Hnf-4(-/-) embryos. Development. 1997;124:279-87 pubmed
    ..Furthermore, specific complementation of Hnf-4(-/-) embryos with tetraploid-derived Hnf-4(+/+) VE rescues their early developmental arrest, showing conclusively that a functional VE is mandatory for gastrulation. ..
  29. Martinez Jimenez C, Kyrmizi I, Cardot P, Gonzalez F, Talianidis I. Hepatocyte nuclear factor 4alpha coordinates a transcription factor network regulating hepatic fatty acid metabolism. Mol Cell Biol. 2010;30:565-77 pubmed publisher
    ..Here, we demonstrate a transcription factor network under the control of hepatocyte nuclear factor 4alpha (HNF4alpha) that coordinates the reciprocal expression of fatty acid transport and metabolizing enzymes during fasting and ..
  30. Taraviras S, Monaghan A, Schutz G, Kelsey G. Characterization of the mouse HNF-4 gene and its expression during mouse embryogenesis. Mech Dev. 1994;48:67-79 pubmed
    ..The complexity of the HSs suggests that multiple elements might contribute to the transcriptional regulation of the HNF-4 gene. ..
  31. Duncan S, Manova K, Chen W, Hoodless P, Weinstein D, Bachvarova R, et al. Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc Natl Acad Sci U S A. 1994;91:7598-602 pubmed
    ..This expression pattern suggests that HNF-4 has a role in the earliest stages of murine postimplantation development as well as in organogenesis. ..
  32. Yin L, Ma H, Ge X, Edwards P, Zhang Y. Hepatic hepatocyte nuclear factor 4? is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb Vasc Biol. 2011;31:328-36 pubmed publisher
    Loss-of-function mutations in human hepatocyte nuclear factor 4? (HNF4?) are associated with maturity-onset diabetes of the young and lipid disorders. However, the mechanisms underlying the lipid disorders are poorly understood...
  33. Molkentin J, Lin Q, Duncan S, Olson E. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 1997;11:1061-72 pubmed
    ..We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP. ..
  34. Nakhei H, Lingott A, Lemm I, Ryffel G. An alternative splice variant of the tissue specific transcription factor HNF4alpha predominates in undifferentiated murine cell types. Nucleic Acids Res. 1998;26:497-504 pubmed
    The transcription factor hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue specific transcription factor mainly expressed in the liver, kidney, intestine and the endocrine pancreas, but is also an essential regulator for early ..
  35. 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 ..
  36. 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 ..
  37. Walesky C, Gunewardena S, Terwilliger E, Edwards G, Borude P, Apte U. Hepatocyte-specific deletion of hepatocyte nuclear factor-4? in adult mice results in increased hepatocyte proliferation. Am J Physiol Gastrointest Liver Physiol. 2013;304:G26-37 pubmed publisher
    Hepatocyte nuclear factor-4? (HNF4?) is known as the master regulator of hepatocyte differentiation. Recent studies indicate that HNF4? may inhibit hepatocyte proliferation via mechanisms that have yet to be identified...
  38. Lazarevich N, Cheremnova O, Varga E, Ovchinnikov D, Kudrjavtseva E, Morozova O, et al. Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology. 2004;39:1038-47 pubmed
    ..These alterations were coupled with a reduced expression of several liver transcription factors including HNF4, a factor essential for hepatocyte differentiation...
  39. Schmidt D, Wilson M, Ballester B, Schwalie P, Brown G, Marshall A, et al. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010;328:1036-40 pubmed publisher
    ..experimentally the genome-wide occupancy of two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in the livers of five vertebrates...
  40. Kanazawa T, Ichii O, Otsuka S, Namiki Y, Hashimoto Y, Kon Y. Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice. J Vet Med Sci. 2011;73:601-7 pubmed
    ..We have previously reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha (Hnf4a) gene induces failure of cellular organization in the condensed mesenchyme (CM) of cultured ..
  41. Geier A, Martin I, Dietrich C, Balasubramaniyan N, Strauch S, Suchy F, et al. Hepatocyte nuclear factor-4alpha is a central transactivator of the mouse Ntcp gene. Am J Physiol Gastrointest Liver Physiol. 2008;295:G226-33 pubmed publisher
    ..Using Hepa 1-6 cells, HNF-4alpha-knockdown resulted in a significant 95% reduction in NTCP mRNA. In conclusion, mouse Ntcp is regulated by HNF-4alpha via a conserved distal cis-element independently of HNF-1alpha. ..
  42. Keng V, Yagi H, Ikawa M, Nagano T, Myint Z, Yamada K, et al. Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage. Biochem Biophys Res Commun. 2000;276:1155-61 pubmed
    ..of transcription factors involved in hepatocyte differentiation, hepatocyte nuclear factor (Hnf)3beta, Hnf6, Hnf4alpha and Hnf1alpha, were restricted to the capsule and internal matrix-like structure in the mutant liver and ..
  43. Shike T, Gohda T, Tanimoto M, Kobayashi M, Makita Y, Funabiki K, et al. Chromosomal mapping of a quantitative trait locus for the development of albuminuria in diabetic KK/Ta mice. Nephrol Dial Transplant. 2005;20:879-85 pubmed
    ..There are potentially important candidate genes that may be relevant to diabetic nephropathy. ..
  44. Choi E, Kraus M, Lemaire L, Yoshimoto M, Vemula S, Potter L, et al. Dual lineage-specific expression of Sox17 during mouse embryogenesis. Stem Cells. 2012;30:2297-308 pubmed publisher
  45. Cossette S, Misra R. The identification of different endothelial cell populations within the mouse proepicardium. Dev Dyn. 2011;240:2344-53 pubmed publisher
    ..These findings indicate that EC exist in the proepicardium before coronary vasculogenesis, and support a model in which there is a heterogeneous origin for EC in the proepicardium. ..
  46. Saandi T, Baraille F, Derbal Wolfrom L, Cattin A, Benahmed F, Martin E, et al. Regulation of the tumor suppressor homeogene Cdx2 by HNF4? in intestinal cancer. Oncogene. 2013;32:3782-8 pubmed publisher
    ..We have previously established that several endodermal transcription factors, including HNF4? and GATA6, are involved in Cdx2 regulation in the normal gut...
  47. Li J, Inoue J, Choi J, Nakamura S, Yan Z, Fushinobu S, et al. Identification of the Flavonoid Luteolin as a Repressor of the Transcription Factor Hepatocyte Nuclear Factor 4α. J Biol Chem. 2015;290:24021-35 pubmed publisher
    Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor that regulates the expression of genes involved in the secretion of apolipoprotein B (apoB)-containing lipoproteins and in glucose metabolism...
  48. Desai S, Tung J, Zhou V, Grenert J, Malato Y, Rezvani M, et al. Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. Hepatology. 2016;64:261-75 pubmed publisher
    ..Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network...
  49. Zhang H, Pu W, Tian X, Huang X, He L, Liu Q, et al. Genetic lineage tracing identifies endocardial origin of liver vasculature. Nat Genet. 2016;48:537-43 pubmed publisher
    ..We conclude that a substantial portion of liver vessels derives from the endocardium and shares a common developmental origin with coronary arteries. ..
  50. Boj S, Petrov D, Ferrer J. Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. PLoS Genet. 2010;6:e1000970 pubmed publisher
    ..The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms ..
  51. Archer A, Sauvaget D, Chauffeton V, Bouchet P, Chambaz J, Pincon Raymond M, et al. Intestinal apolipoprotein A-IV gene transcription is controlled by two hormone-responsive elements: a role for hepatic nuclear factor-4 isoforms. Mol Endocrinol. 2005;19:2320-34 pubmed
    ..The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts. ..
  52. Guo H, Wei J, Inoue Y, Gonzalez F, Kuo P. Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes. Am J Physiol Cell Physiol. 2003;284:C1090-9 pubmed
    ..A unique pattern of phosphorylation determines HNF-4alpha activity as a trans-activator of IL-1beta-mediated hepatocyte iNOS expression in the presence of oxidative stress. ..
  53. Margagliotti S, Clotman F, Pierreux C, Beaudry J, Jacquemin P, Rousseau G, et al. The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration. Dev Biol. 2007;311:579-89 pubmed
    ..This network operating at the onset of liver development contains candidate genes for investigation of liver carcinogenesis. ..
  54. Rodgers J, Lerin C, Haas W, Gygi S, Spiegelman B, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434:113-8 pubmed
    ..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan. ..
  55. Stanulovic V, Kyrmizi I, Kruithof de Julio M, Hoogenkamp M, Vermeulen J, Ruijter J, et al. Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes. Hepatology. 2007;45:433-44 pubmed
    ..The transcription factor hepatic nuclear-factor4alpha (HNF4alpha) is associated with 12% of the genes in adult liver, but its involvement in zonation of gene expression has not ..
  56. Clotman F, Lannoy V, Reber M, Cereghini S, Cassiman D, Jacquemin P, et al. The onecut transcription factor HNF6 is required for normal development of the biliary tract. Development. 2002;129:1819-28 pubmed
    ..We conclude that HNF6 is essential for differentiation and morphogenesis of the biliary tract and that intrahepatic bile duct development is controlled by a HNF6-->HNF1beta cascade...
  57. Caron S, Huaman Samanez C, Dehondt H, Ploton M, Briand O, Lien F, et al. Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol Cell Biol. 2013;33:2202-11 pubmed publisher
    ..L4L3 region of the L-PK promoter, known to bind the transcription factors ChREBP and hepatocyte nuclear factor 4? (HNF4?). FXR interacts directly with ChREBP and HNF4? proteins...
  58. Wang L, Wansleeben C, Zhao S, Miao P, Paschen W, Yang W. SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development. EMBO Rep. 2014;15:878-85 pubmed publisher
    ..Thus, our findings suggest that expression levels and not functional differences between SUMO2 and SUMO3 are critical for normal embryogenesis. ..
  59. Ang S, Wierda A, Wong D, Stevens K, Cascio S, Rossant J, et al. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993;119:1301-15 pubmed
    ..HFH-E5.1 is highly similar in structure and expression profile to the Drosophila HFH gene FD4, suggesting that HFH family members have different, evolutionarily conserved roles in development. ..
  60. Ohguchi H, Tanaka T, Uchida A, Magoori K, Kudo H, Kim I, et al. 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. Mol Cell Biol. 2008;28:3917-31 pubmed publisher
    ..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...
  61. 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...
  62. Konstandi M, Shah Y, Matsubara T, Gonzalez F. Role of PPAR? and HNF4? in stress-mediated alterations in lipid homeostasis. PLoS ONE. 2013;8:e70675 pubmed publisher
    ..This study investigated the role of stress and adrenergic receptor (AR)-related pathways in PPAR? and HNF4? regulation and signaling in mice following repeated restraint stress or treatment with AR-antagonists administered ..
  63. Saéz López C, Rivera Giménez M, Hernández C, Simó R, Selva D. SHBG-C57BL/ksJ-db/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development. Endocrinology. 2015;156:4571-81 pubmed publisher
    ..Future research using this unique mouse model will determine the role of SHBG in the development and progression of obesity, type 2 diabetes, or fatty liver disease. ..
  64. Puigserver P, Rhee J, Donovan J, Walkey C, Yoon J, Oriente F, et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature. 2003;423:550-5 pubmed
    ..We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. ..
  65. Gougelet A, Torre C, Veber P, Sartor C, Bachelot L, Denechaud P, et al. T-cell factor 4 and ?-catenin chromatin occupancies pattern zonal liver metabolism in mice. Hepatology. 2014;59:2344-57 pubmed publisher
    ..Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by ?-catenin, partly through xenobiotic nuclear receptors...
  66. 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
    ..correlated with four liver-enriched transcription factors (LETFs)-hepatocyte nuclear factor (HNF) 1?, HNF3?, HNF4?, and CCAAT/enhancer-binding protein (C/EBP) ?-in the livers of developing mouse embryos and in human ..
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    ..These results are the first to elucidate the diverse role of YY1 during gastrulation in vivo. ..
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    ..This explains why cystic EBs reproduce the imprinted expression seen in the embryo but not that seen in the ysE. ..