Genomes and Genes
Gene Symbol: Hnf1a
Description: HNF1 homeobox A
Alias: HNF1, LF-B1, Lfb1, Tcf1, hepatocyte nuclear factor 1-alpha, HNF-1-alpha, HNF-1A, LF-B1, hepatic nuclear factor (HNF1): albumin proximal factor, also TCF1, TCF-1, Transcription factor 1, hepatic, albumin proximal factor, hepatic nuclear factor 1, hepatic nuclear factor-1-alpha, liver-specific transcription factor LF-B1
- Pontoglio M, Prie D, Cheret C, Doyen A, Leroy C, Froguel P, et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep. 2000;1:359-65 pubmed..Our results show that HNF1alpha directly controls SGLT2 gene expression. Together these data indicate that HNF1alpha plays a key role in glucose homeostasis in mammals. ..
- Dukes I, Sreenan S, Roe M, Levisetti M, Zhou Y, Ostrega D, et al. Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice. J Biol Chem. 1998;273:24457-64 pubmed..We conclude that hepatocyte nuclear factor-1alpha diabetes results from defective beta-cell glycolytic signaling, which is potentially correctable using substrates that bypass the defect. ..
- Chouard T, Blumenfeld M, Bach I, Vandekerckhove J, Cereghini S, Yaniv M. A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Nucleic Acids Res. 1990;18:5853-63 pubmedb>Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes...
- Dohda T, Kaneoka H, Inayoshi Y, Kamihira M, Miyake K, Iijima S. Transcriptional coactivators CBP and p300 cooperatively enhance HNF-1alpha-mediated expression of the albumin gene in hepatocytes. J Biochem. 2004;136:313-9 pubmed..In addition, inhibition of CBP or p300 using small interfering RNAs (siRNAs) resulted in a reduction in albumin expression. These results suggest that both CBP and p300 are required for enhanced expression of albumin. ..
- Toor A, Lund T, Miller J. T-cell factor-1 expression during human natural killer cell development and in circulating CD56(+) bright natural killer cells. Exp Hematol. 2001;29:499-506 pubmed
- Freitas H, Anhê G, Melo K, Okamoto M, Oliveira Souza M, Bordin S, et al. Na(+) -glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology. 2008;149:717-24 pubmed..Our demonstration that HNF-1alpha binds DNA that encodes SGLT2 supports the hypothesis that HNF-1alpha, as a modulator of SGLT2 expression, may be involved in diabetic kidney disease. ..
- Harries L, Brown J, Gloyn A. Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PLoS ONE. 2009;4:e7855 pubmed publisherThe HNF1A, HNF1B and HNF4A genes are part of an autoregulatory network in mammalian pancreas, liver, kidney and gut...
- Bonner C, Farrelly A, Concannon C, Dussmann H, Baquie M, Virard I, et al. Bone morphogenetic protein 3 controls insulin gene expression and is down-regulated in INS-1 cells inducibly expressing a hepatocyte nuclear factor 1A-maturity-onset diabetes of the young mutation. J Biol Chem. 2011;286:25719-28 pubmed publisherInactivating mutations in the transcription factor hepatocyte nuclear factor (HNF) 1A cause HNF1A-maturity-onset diabetes of the young (HNF1A-MODY), the most common monogenic form of diabetes...
- Kirkpatrick C, Wiederkehr A, Baquie M, Akhmedov D, Wang H, Gauthier B, et al. Hepatic nuclear factor 1alpha (HNF1alpha) dysfunction down-regulates X-box-binding protein 1 (XBP1) and sensitizes beta-cells to endoplasmic reticulum stress. J Biol Chem. 2011;286:32300-12 pubmed publisher..We have used an insulin-secreting cell line with inducible expression of dominant negative (DN) HNF1?, a transcription factor vital for correct ?-cell development and function, to show that HNF1? is required for Xbp1 ..
- Jakowlew S, Moody T, You L, Mariano J. Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis. Mol Carcinog. 1998;22:46-56 pubmed..These data suggest that a decrease in expression of TGF-beta RII may contribute to autonomous cell growth and may play an important role in mouse lung carcinogenesis induced by urethane. ..
- Luco R, Maestro M, del Pozo N, Philbrick W, de la Ossa P, Ferrer J. A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious. Diabetes. 2006;55:2202-11 pubmed..This finding illustrates the paramount importance of using the correct concentration of a beta-cell transcription factor in both gene therapy and artificial differentiation strategies. ..
- Miura N, Iwai K, Miyamoto I. Immunological characterization of hepatocyte nuclear factor 1 protein: appearance of hepatocyte nuclear factor 1 protein in developing mouse embryos. Eur J Cell Biol. 1993;60:376-82 pubmed
- van de Wetering M, Oosterwegel M, Dooijes D, Clevers H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 1991;10:123-32 pubmed..These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype. ..
- 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. ..
- Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387-98 pubmed publisher..Since then, further components of the Wnt pathway have been identified and their epistatic relationships have been defined. This article is a Timeline of crucial discoveries about the components and functions of this essential pathway. ..
- Piaggio G, Tomei L, Toniatti C, De Francesco R, Gerstner J, Cortese R. LFB1/HNF1 acts as a repressor of its own transcription. Nucleic Acids Res. 1994;22:4284-90 pubmedLFB1/HNF1 is a hepatocyte-enriched trans-activator involved in the regulation of many liver-specific genes. We report the cloning and characterization of a rat genomic DNA fragment containing about 3...
- Ellard S, Thomas K, Edghill E, Owens M, Ambye L, Cropper J, et al. Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young. Diabetologia. 2007;50:2313-7 pubmedHeterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY...
- Karges B, Bergmann C, Scholl K, Heinze E, Rasche F, Zerres K, et al. Digenic inheritance of hepatocyte nuclear factor-1alpha and -1beta with maturity-onset diabetes of the young, polycystic thyroid, and urogenital malformations. Diabetes Care. 2007;30:1613-4 pubmed
- Bellanne Chantelot C, Carette C, Riveline J, Valéro R, Gautier J, Larger E, et al. The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. Diabetes. 2008;57:503-8 pubmed..and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-alpha (HNF1A) gene mutation...
- Sucajtys Szulc E, Szolkiewicz M, Swierczynski J, Rutkowski B. Up-regulation of Hnf1Î± gene expression in the liver of rats with experimentally induced chronic renal failure - A possible link between circulating PCSK9 and triacylglycerol concentrations. Atherosclerosis. 2016;248:17-26 pubmed publisherThe aim of this study was to verify if an increase in Hnf1Î± gene expression could be a possible link between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) and TAGs concentrations in chronic renal failure (CRF)...
- 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. ..
- Xu E, Perlina A, Vu H, TROTH S, Brennan R, Aslamkhan A, et al. Integrated pathway analysis of rat urine metabolic profiles and kidney transcriptomic profiles to elucidate the systems toxicology of model nephrotoxicants. Chem Res Toxicol. 2008;21:1548-61 pubmed publisher..Furthermore, this analysis suggests that renal transcription factors HNF1alpha, HNF1beta, and HIF-1 might be the central mediators of drug-induced kidney injury and adaptive response pathways. ..
- de Simone V, De Magistris L, Lazzaro D, Gerstner J, Monaci P, Nicosia A, et al. LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia. EMBO J. 1991;10:1435-43 pubmed..The first 315 amino acids of LFB3 are highly homologous to the DNA binding domain of LFB1, a regulatory protein involved in the expression of several liver-specific genes...
- Mendel D, Khavari P, Conley P, Graves M, Hansen L, Admon A, et al. Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. Science. 1991;254:1762-7 pubmed..These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex. ..
- Schott O, Billeter M, Leiting B, Wider G, Wuthrich K. The NMR solution structure of the non-classical homeodomain from the rat liver LFB1/HNF1 transcription factor. J Mol Biol. 1997;267:673-83 pubmedThe nuclear magnetic resonance (NMR) solution structure of the non-classical homeodomain from the rat liver LFB1/HNF1 transcription factor was determined with the program DIANA from an input of 1356 nuclear Overhauser enhancement (NOE) ..
- Yoshiuchi I, Yamagata K, Yang Q, Iwahashi H, Okita K, Yamamoto K, et al. Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization. Diabetologia. 1999;42:621-6 pubmed..Mutations in the HNF-1alpha gene may affect the normal islet function by different molecular mechanisms. ..
- Galceran J, Miyashita Lin E, Devaney E, Rubenstein J, Grosschedl R. Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development. 2000;127:469-82 pubmed..Thus, LEF1 regulates the generation of dentate gyrus granule cells, and together with other LEF1/TCF proteins, the development of the hippocampus. ..
- Yang X, Jansson P, Nagaev I, Jack M, Carvalho E, Sunnerhagen K, et al. Evidence of impaired adipogenesis in insulin resistance. Biochem Biophys Res Commun. 2004;317:1045-51 pubmed..The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the ..
- Miura N, Wanaka A, Tohyama M, Tanaka K. MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme. FEBS Lett. 1993;326:171-6 pubmed..Our results suggest that MFH-1 might be involved in the formation of special mesenchymal tissues. ..
- Farrelly A, Wobser H, Bonner C, Anguissola S, Rehm M, Concannon C, et al. Early loss of mammalian target of rapamycin complex 1 (mTORC1) signalling and reduction in cell size during dominant-negative suppression of hepatic nuclear factor 1-alpha (HNF1A) function in INS-1 insulinoma cells. Diabetologia. 2009;52:136-44 pubmed publisherMutations in the HNF1A (previously known as TCF1) gene encoding hepatocyte nuclear factor-1alpha (HNF1A) lead to the development of maturity-onset diabetes of the young, type 3 (HNF1A-MODY), characterised by impaired insulin secretion ..
- Rose R, Endrizzi J, Cronk J, Holton J, Alber T. High-resolution structure of the HNF-1alpha dimerization domain. Biochemistry. 2000;39:15062-70 pubmed..Mutations in HNF-1alpha are associated with maturity-onset diabetes of the young type 3 (MODY3), and the structure of HNF-p1 provides insights into the effects of three MODY3 mutations. ..
- Nammo T, Yamagata K, Hamaoka R, Zhu Q, Akiyama T, Gonzalez F, et al. Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas. Diabetologia. 2002;45:1142-53 pubmed..HNF-1alpha is expressed by both endocrine cells and exocrine cells of the pancreas from the foetal stage along with other transcription factors, so HNF-1alpha might play a role during development. ..
- Pare J, Malenfant D, Courtemanche C, Jacob Wagner M, Roy S, Allard D, et al. The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem. 2004;279:21206-16 pubmed..The FTF-lacZ mouse establishes a central role for FTF in developmental, nutritive, and metabolic functions from early embryogenesis through adulthood. ..
- Jackson A, Cassell P, North B, Vijayaraghavan S, Gelding S, Ramachandran A, et al. Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population. Diabetes. 2004;53:2122-5 pubmedThe neurogenic differentiation-1 (NEUROD1), neurogenin-3 (NEUROG3), and hepatic nuclear factor-1alpha (TCF1) genes are interacting transcription factors implicated in controlling islet cell development and insulin secretion...
- Hiesberger T, Shao X, Gourley E, Reimann A, Pontoglio M, Igarashi P. Role of the hepatocyte nuclear factor-1beta (HNF-1beta) C-terminal domain in Pkhd1 (ARPKD) gene transcription and renal cystogenesis. J Biol Chem. 2005;280:10578-86 pubmed..Expression of HNF-1alpha in proximal tubules may protect against cystogenesis. ..
- Wu G, Bohn S, Ryffel G. The HNF1beta transcription factor has several domains involved in nephrogenesis and partially rescues Pax8/lim1-induced kidney malformations. Eur J Biochem. 2004;271:3715-28 pubmed..We conclude that HNF1beta has some distinct morphogenetic properties during nephrogenesis. ..
- Streeper R, Eaton E, Ebert D, Chapman S, Svitek C, O Brien R. Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. Proc Natl Acad Sci U S A. 1998;95:9208-13 pubmed..The potential role of G6Pase overexpression in the pathophysiology of MODY3 and 5, rare forms of diabetes caused by hepatocyte nuclear factor-1 mutations, is discussed. ..
- Ceska T, Lamers M, Monaci P, Nicosia A, Cortese R, Suck D. The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding. EMBO J. 1993;12:1805-10 pubmedThe transcription factor LFB1/HNF1 from rat liver nuclei is a 628 amino acid protein that functions as a dimer binding to the inverted palindrome GTTAATN-ATTAAC consensus site...
- 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. ..
- Kamiya A, Inoue Y, Kodama T, Gonzalez F. Hepatocyte nuclear factors 1alpha and 4alpha control expression of proline oxidase in adult liver. FEBS Lett. 2004;578:63-8 pubmed..These results suggested that HNF4alpha and HNF1alpha regulate proline metabolism in adult liver. ..
- Galceran J, Farinas I, Depew M, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13:709-17 pubmed..However, targeted gene inactivations of Lef1, Tcf1, or Tcf4 in the mouse do not produce phenotypes that mimic any known Wnt mutation...
- Hu C, Perlmutter D. Regulation of alpha1-antitrypsin gene expression in human intestinal epithelial cell line caco-2 by HNF-1alpha and HNF-4. Am J Physiol. 1999;276:G1181-94 pubmed..Together, these results provide evidence that HNF-1alpha and HNF-4 play a role in the mechanism by which the alpha1-AT gene is upregulated during enterocyte differentiation in the model Caco-2 cell system. ..
- Mouchel N, Henstra S, McCarthy V, Williams S, Phylactides M, Harris A. HNF1alpha is involved in tissue-specific regulation of CFTR gene expression. Biochem J. 2004;378:909-18 pubmed..In contrast, antisense inhibition of HNF1 alpha transcription decreased the CFTR mRNA levels...
- Pramfalk C, Davis M, Eriksson M, Rudel L, Parini P. Control of ACAT2 liver expression by HNF1. J Lipid Res. 2005;46:1868-76 pubmed..We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human ..
- Muppala V, Lin C, Lee Y. The role of HNF-1alpha in controlling hepatic catalase activity. Mol Pharmacol. 2000;57:93-100 pubmed..Furthermore, our results of cell transfection and luciferase reporter assay indicated that the mouse ferrochelatase promoter could be trans-activated directly by HNF-1alpha. ..
- Wolfrum C, Poy M, Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med. 2005;11:418-22 pubmed
- Leiting B, De Francesco R, Tomei L, Cortese R, Otting G, Wuthrich K. The three-dimensional NMR-solution structure of the polypeptide fragment 195-286 of the LFB1/HNF1 transcription factor from rat liver comprises a nonclassical homeodomain. EMBO J. 1993;12:1797-803 pubmedThe three-dimensional backbone fold of a polypeptide fragment from the rat LFB1/HNF1 transcription factor was determined by nuclear magnetic resonance (NMR) spectroscopy in solution...
- Parrizas M, Maestro M, Boj S, Paniagua A, Casamitjana R, Gomis R, et al. Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets. Mol Cell Biol. 2001;21:3234-43 pubmedMutations in the gene encoding hepatic nuclear factor 1-alpha (HNF1-alpha) cause a subtype of human diabetes resulting from selective pancreatic beta-cell dysfunction...
- Prajapati K, Sharma S, Roy N. Hepatocyte nuclear factor-1alpha mediated upregulation of albumin expression in focal ischemic rat brain. Neurol Res. 2012;34:25-31 pubmed publisher..Moreover, an increased interaction of HNF-1alpha with p300 and albumin promoter seems to be responsible for overexpression of albumin in ischemic conditions. ..
- Glass D, Bialek P, Ahn J, Starbuck M, Patel M, Clevers H, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8:751-64 pubmed