Genomes and Genes
hepatocyte nuclear factor 1
Summary: A transcription factor and homeodomain protein that regulates the expression of a large set of hepatic proteins including SERUM ALBUMIN; beta-fibrinogen; and ALPHA 1-ANTITRYPSIN. It is composed of hetero- or homo-dimers of HEPATOCYTE NUCLEAR FACTOR 1-ALPHA and HEPATOCYTE NUCLEAR FACTOR 1-BETA.
- Baumhueter S, Mendel D, Conley P, Kuo C, Turk C, Graves M, et al. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Genes Dev. 1990;4:372-9 pubmed..These data indicate that HNF-1 is a more broadly acting transcription factor than has been indicated by previous work. ..
- Frain M, Swart G, Monaci P, Nicosia A, Stampfli S, Frank R, et al. The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain. Cell. 1989;59:145-57 pubmed..The distribution of LF-B1 mRNA is restricted to liver, which correlates with the tissue-specific expression of its target genes. ..
- Leu J, Crissey M, Leu J, Ciliberto G, Taub R. Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury. Mol Cell Biol. 2001;21:414-24 pubmed..In both hepatic and nonhepatic cells, IL-6 -mediated IGFBP-1 promoter activation was via an intact hepatocyte nuclear factor 1 (HNF-1) site and was dependent on the presence of endogenous liver factor HNF-1 and induced factors ..
- Pontoglio M. Hepatocyte nuclear factor 1, a transcription factor at the crossroads of glucose homeostasis. J Am Soc Nephrol. 2000;11 Suppl 16:S140-3 pubmedb>Hepatocyte nuclear factor 1 (HNF1) is a transcription factor involved in the regulation of a large set of hepatic genes, including albumin, beta-fibrinogen, and alpha1-antitrypsin...
- Bulman M, Harries L, Hansen T, Shepherd M, Kelly W, Hattersley A, et al. Abnormal splicing of hepatocyte nuclear factor 1 alpha in maturity-onset diabetes of the young. Diabetologia. 2002;45:1463-7 pubmed..This analysis of the mRNA is required to define mutational mechanisms and confirm pathogenic status. ..
- Ishii Y, Hansen A, Mackenzie P. Octamer transcription factor-1 enhances hepatic nuclear factor-1alpha-mediated activation of the human UDP glucuronosyltransferase 2B7 promoter. Mol Pharmacol. 2000;57:940-7 pubmed..This interaction between HNF1alpha and Oct-1 may fine-tune UGT2B7 expression. ..
- Ryffel G. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. J Mol Endocrinol. 2001;27:11-29 pubmed..This review summarizes the main features of these transcription factors and discusses potential events leading to the specific disease phenotypes. ..
- Kim F, Sing l A, Kaneko T, Bieman M, Stallwood N, Sadl V, et al. The vHNF1 homeodomain protein establishes early rhombomere identity by direct regulation of Kreisler expression. Mech Dev. 2005;122:1300-9 pubmed..variant Hepatocyte Nuclear Factor 1 (vHNF1/HNF1beta/LF-3B) is transiently expressed in the r5/r6 domain of 0-10 somite stage embryos and a ..
- Mosialou I, Krasagakis K, Kardassis D. Opposite regulation of the human apolipoprotein M gene by hepatocyte nuclear factor 1 and Jun transcription factors. J Biol Chem. 2011;286:17259-69 pubmed publisher..the human apoM promoter harbors a dual specificity regulatory element in the proximal region that binds hepatocyte nuclear factor 1 (HNF-1) and members of the AP-1 family of pro-inflammatory transcription factors (c-Jun and JunB)...
- Lee Y, Sauer B, Gonzalez F. Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse. Mol Cell Biol. 1998;18:3059-68 pubmedMice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) were produced by use of the Cre-loxP recombination system...
- Gong H, Lin C, Chen M, Hu M, Lin G, Zhou Y, et al. Two distinct teleost hepatocyte nuclear factor 1 genes, hnf1alpha/tcf1 and hnf1beta/tcf2, abundantly expressed in liver, pancreas, gut and kidney of zebrafish. Gene. 2004;338:35-46 pubmedTwo distinct forms of zebrafish hepatocyte nuclear factor 1 (hnf1) were identified and referred to as hnf1alpha/tcf1 and hnf1beta/tcf2. Both hnf1 genes were shown to be expressed abundantly in liver, pancreas, gut and kidney...
- Jung D, Kullak Ublick G. Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression. Hepatology. 2003;37:622-31 pubmed..This explains the suppressive effect of bile acids on the OATP-C gene promoter, leading to decreased expression in cholestatic liver disease. ..
- Gregory P, Lewinsky R, Gardner Stephen D, Mackenzie P. Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 genes by hepatocyte nuclear factor 1alpha and the caudal-related homeodomain protein 2. Mol Pharmacol. 2004;65:953-63 pubmed..sites for the intestine-specific transcription factor, caudal-related homeodomain protein 2 (Cdx2), and hepatocyte nuclear factor 1 (HNF1) were identified...
- Emens L, Landers D, Moss L. Hepatocyte nuclear factor 1 alpha is expressed in a hamster insulinoma line and transactivates the rat insulin I gene. Proc Natl Acad Sci U S A. 1992;89:7300-4 pubmed..A portion of the FLAT element bears considerable sequence similarity to the consensus binding site for hepatocyte nuclear factor 1 alpha (HNF1 alpha; LF-B1) a liver-enriched homeodomain-containing transcription factor...
- 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. ..
- Locker J, Ghosh D, Luc P, Zheng J. Definition and prediction of the full range of transcription factor binding sites--the hepatocyte nuclear factor 1 dimeric site. Nucleic Acids Res. 2002;30:3809-17 pubmed..The experimental process was defined by studying hepatocyte nuclear factor 1 (HNF1), which binds DNA as a dimer on two inverted-repeat 7-bp half sites separated by one base...
- Gardner Stephen D, Mackenzie P. Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4alpha. Pharmacogenet Genomics. 2007;17:25-36 pubmed..4alpha-mediated transcription from the human UGT1A9 promoter was discovered to be entirely dependent on hepatocyte nuclear factor 1. We have established that two hepatocyte nuclear factor 1-binding elements are involved in this ..
- Cheung C, Akiyama T, Kudo G, Gonzalez F. Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1alpha)-deficient mice. Biochem Pharmacol. 2003;66:2011-20 pubmedb>Hepatocyte nuclear factor 1 alpha (HNF1alpha) is a liver enriched homeodomain-containing transcription factor that has been shown to transactivate the promoters of several cytochrome P450 (CYP) genes, including CYP2E1, CYP1A2, CYP7A1, ..
- Tomassetti A, Mangiarotti F, Mazzi M, Sforzini S, Miotti S, Galmozzi E, et al. The variant hepatocyte nuclear factor 1 activates the P1 promoter of the human alpha-folate receptor gene in ovarian carcinoma. Cancer Res. 2003;63:696-704 pubmed..Analysis of RNA from various cell lines and surgical specimens confirmed that vHNF1 is expressed in ovarian carcinomas. Thus, vHNF1 regulates tissue-specific transcription in ovarian carcinoma. ..
- Bernard P, Goudonnet H, Artur Y, Desvergne B, Wahli W. Activation of the mouse TATA-less and human TATA-containing UDP-glucuronosyltransferase 1A1 promoters by hepatocyte nuclear factor 1. Mol Pharmacol. 1999;56:526-36 pubmed..Using the electromobility shift and DNase I footprinting experiments, we have identified a hepatocyte nuclear factor 1-binding site in the mouse UGT1A1 promoter that confers responsiveness to both factors HNF1alpha and ..
- Pontoglio M, Sreenan S, Roe M, Pugh W, Ostrega D, Doyen A, et al. Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. J Clin Invest. 1998;101:2215-22 pubmed..These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function. ..
- Yamagata K, Oda N, Kaisaki P, Menzel S, Furuta H, Vaxillaire M, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature. 1996;384:455-8 pubmed..HNF-1alpha is a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene. ..
- Laurent Puig P, Plomteux O, Bluteau O, Zinzindohoue F, Jeannot E, Dahan K, et al. Frequent mutations of hepatocyte nuclear factor 1 in colorectal cancer with microsatellite instability. Gastroenterology. 2003;124:1311-4 pubmedThe TCF1 gene encoding hepatocyte nuclear factor 1 alpha (HNF1), a transcription factor germline mutated in patients with maturity-onset diabetes of the young type 3, was recently found to be frequently inactivated by biallelic ..
- 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 pubmed..Together with its property to dimerize in the presence or absence of DNA, these features place HNF1 as the prototype of a novel subclass of transcription factors distantly related to homeoproteins. ..
- Shih D, Screenan S, Munoz K, Philipson L, Pontoglio M, Yaniv M, et al. Loss of HNF-1alpha function in mice leads to abnormal expression of genes involved in pancreatic islet development and metabolism. Diabetes. 2001;50:2472-80 pubmed..Our results indicate that loss of Hnf-1alpha function leads to altered expression of genes involved in glucose-stimulated insulin secretion, insulin synthesis, and beta-cell differentiation. ..
- Aragon F, Vázquez Echeverría C, Ulloa E, Reber M, Cereghini S, Alsina B, et al. vHnf1 regulates specification of caudal rhombomere identity in the chick hindbrain. Dev Dyn. 2005;234:567-76 pubmed..However, our data suggest differences in the vHnf1 downstream cascade in different vertebrates. ..
- Frayling T, Bulman M, Appleton M, Hattersley A, Ellard S. A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes. Hum Genet. 1997;101:351-4 pubmed..Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene have recently been shown to cause MODY...
- Lerman Garber I. [Early-onset diabetes in the Mexican population: prevalence, genetic and metabolic features]. Rev Invest Clin. 2003;55:305-7 pubmed
- Frayling T, McCarthy M, Walker M, Levy J, O Rahilly S, Hitman G, et al. No evidence for linkage at candidate type 2 diabetes susceptibility loci on chromosomes 12 and 20 in United Kingdom Caucasians. J Clin Endocrinol Metab. 2000;85:853-7 pubmed..We have not confirmed in United Kingdom Caucasians the evidence for linkage previously reported on 12q and 20q. Our results highlight further the problems of replicating previous positive linkage results across different ethnic groups. ..
- Friedlander G, Runembert I, Vrtovsnik F, Terzi F. Renal tubular cells cultured from genetically modified animals. Exp Nephrol. 1999;7:407-12 pubmed..These observations illustrate the interest and limits of the in vitro models for studying renal function in transgenic animals. ..
- Holewa B, Strandmann E, Zapp D, Lorenz P, Ryffel G. Transcriptional hierarchy in Xenopus embryogenesis: HNF4 a maternal factor involved in the developmental activation of the gene encoding the tissue specific transcription factor HNF1 alpha (LFB1). Mech Dev. 1996;54:45-57 pubmed
- Saudek F, Pruhova S, Boucek P, Lebl J, Adamec M, Ek J, et al. Maturity-onset diabetes of the young with end-stage nephropathy: a new indication for simultaneous pancreas and kidney transplantation?. Transplantation. 2004;77:1298-301 pubmed..A hyperglycemic clamp test showed a normal beta-cell function. Identification of MODY3 among all C-peptide-positive patients with advanced diabetic nephropathy might help to select a specific group profiting from SPK. ..
- Swenson E, Guest I, Ilic Z, Mazzeo Helgevold M, Lizardi P, Hardiman C, et al. Hepatocyte nuclear factor-1 as marker of epithelial phenotype reveals marrow-derived hepatocytes, but not duct cells, after liver injury in mice. Stem Cells. 2008;26:1768-77 pubmed publisher..The use of a nuclear marker of mature hepatocytes or cholangiocytes, such as HNF1, improves discrimination of marrow-derived epithelial cells in tissue sections. ..
- van Wering H, Huibregtse I, van der Zwan S, de Bie M, Dowling L, Boudreau F, et al. Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter. J Biol Chem. 2002;277:27659-67 pubmed..Parallel mechanisms in other tissues as well as in Drosophila suggest that zinc finger/homeodomain interactions are an efficient pathway of cooperative activation of gene transcription that has been conserved throughout evolution. ..
- Tomassetti A, De Santis G, Castellano G, Miotti S, Mazzi M, Tomasoni D, et al. Variant HNF1 modulates epithelial plasticity of normal and transformed ovary cells. Neoplasia. 2008;10:1481-92, 3p following 1492 pubmed..The variant isoform of the hepatocyte nuclear factor 1 (vHNF1) is a transcription factor involved in the development of tissues derived from the müllerian ..
- Kobayashi H, Kajihara H, Yamada Y, Tanase Y, Kanayama S, Furukawa N, et al. Risk of carcinoma in women with ovarian endometrioma. Front Biosci (Elite Ed). 2011;3:529-39 pubmed..This review summarizes recent advances in the understanding of epidemiology, carcinogenesis, pathogenesis, and pathophysiology of endometriosis-associated EOC; and a possible novel model is proposed. ..
- Bach I, Mattei M, Cereghini S, Yaniv M. Two members of an HNF1 homeoprotein family are expressed in human liver. Nucleic Acids Res. 1991;19:3553-9 pubmed..We assigned the vHNF-1 gene to human chromosome 17 and murine chromosome 11. These chromosomal localizations differ from that of the HNF-1 gene indicating that both genes are not clustered on the genome. ..
- Geier A, Kim S, Gerloff T, Dietrich C, Lammert F, Karpen S, et al. Hepatobiliary organic anion transporters are differentially regulated in acute toxic liver injury induced by carbon tetrachloride. J Hepatol. 2002;37:198-205 pubmed..Binding activity of Ntcp transactivators (hepatocyte nuclear factor 1 alpha (HNF1alpha) and CAAT enhancer binding protein alpha (C/EBPalpha) were reduced by 24h, whereas ..
- Lee Y, Magnuson M, Muppala V, Chen S. Liver-specific reactivation of the inactivated Hnf-1alpha gene: elimination of liver dysfunction to establish a mouse MODY3 model. Mol Cell Biol. 2003;23:923-32 pubmedMice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) develop dwarfism, liver dysfunction, and type 2 diabetes mellitus. Liver dysfunction in HNF-1alpha-null mice includes severe hepatic glycogen accumulation and dyslipidemia...
- Bonham K, Ritchie S, Dehm S, Snyder K, Boyd F. An alternative, human SRC promoter and its regulation by hepatic nuclear factor-1alpha. J Biol Chem. 2000;275:37604-11 pubmed
- Boukaftane Y, Mitchell G. Cloning and characterization of the human mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase gene. Gene. 1997;195:121-6 pubmed..The 5' flanking region contains potential binding sites for TATA-binding protein, Sp1, nuclear factor 1 (NF1), CAAT-box binding protein (C/EBP), hepatocyte nuclear factors 1 and 5 (HNF1, HNF5) and activator proteins 1 and 2 (AP1, AP2). ..
- Hattersley A. Diagnosis of maturity-onset diabetes of the young in the pediatric diabetes clinic. J Pediatr Endocrinol Metab. 2000;13 Suppl 6:1411-7 pubmed
- Heibel S, Ah Mew N, Caldovic L, Daikhin Y, Yudkoff M, Tuchman M. N-carbamylglutamate enhancement of ureagenesis leads to discovery of a novel deleterious mutation in a newly defined enhancer of the NAGS gene and to effective therapy. Hum Mutat. 2011;32:1153-60 pubmed publisher..Oral daily NCG therapy restored ureagenesis in this patient, normalizing her biochemical markers, and allowing discontinuation of alternate pathway therapy and normalization of her diet with no recurrence of hyperammonemia. Inc. ..
- Pastore A, De Francesco R, Barbato G, Castiglione Morelli M, Motta A, Cortese R. 1H resonance assignment and secondary structure determination of the dimerization domain of transcription factor LFB1. Biochemistry. 1991;30:148-53 pubmed..Although further studies are still necessary to determine the 3D structure of the peptide, we can exclude the possibility of a coiled-coil structure. ..
- Bernier D, Thomassin H, Allard D, Guertin M, Hamel D, Blaquiere M, et al. Functional analysis of developmentally regulated chromatin-hypersensitive domains carrying the alpha 1-fetoprotein gene promoter and the albumin/alpha 1-fetoprotein intergenic enhancer. Mol Cell Biol. 1993;13:1619-33 pubmed..Factor FTF seems to be the key regulator of AFP gene-specific functions in carcinoembryonic states. ..
- Cronk J, Endrizzi J, Alber T. High-resolution structures of the bifunctional enzyme and transcriptional coactivator DCoH and its complex with a product analogue. Protein Sci. 1996;5:1963-72 pubmedDCoH, the dimerization cofactor of hepatocyte nuclear factor 1 (HNF-1), functions as both a transcriptional coactivator and a pterin dehydratase...
- Soumounou Y, Gauthier C, Tenenhouse H. Murine and human type I Na-phosphate cotransporter genes: structure and promoter activity. Am J Physiol Renal Physiol. 2001;281:F1082-91 pubmed..Other well-characterized cis-acting elements were identified in the Npt1 promoter. We suggest that Npt1 expression is transcriptionally regulated and provide a basis for the investigation of Npt1 function by targeted mutagenesis...
- Weng J, Lehto M, Berglund A, Groop L. An automated fluorescent single strand conformation polymorphism technique for high throughput mutation screening. Chin Med J (Engl). 2001;114:1147-50 pubmed..This fluorescence-based PCR single strand conformation polymorphism technique represents a simple, non-hazardous, time-saving and sensitive method for high throughput mutation detection. ..
- Prisco F, Iafusco D. Why is the ADA classification of diabetes mellitus not always applied?. Diabetologia. 2002;45:747 pubmed
- Zahedi K, Prada A, Mulligan A, Prada J, Davis A. Normal transcription of the C1 inhibitor gene is dependent upon a polypurine-polypyrimidine region within the promoter. Inflammation. 2002;26:183-91 pubmed..Southwestern blot analysis detected four bands (M(r)s -130, 75, 65 and 20 kDa). These data suggest that the -98 to -9 region of the C1INH promoter interacts with at least four proteins, one of which is HNF-1alpha. ..
- Cervin C, Orho Melander M, Ridderstrale M, Lehto M, Barg S, Groop L, et al. Characterization of a naturally occurring mutation (L107I) in the HNF1 alpha (MODY3) gene. Diabetologia. 2002;45:1703-8 pubmed..type 3 (MODY3) is a monogenic form of diabetes mellitus caused by mutations in the gene encoding for hepatocyte nuclear factor 1 alpha, HNF1 alpha...
- Su J, Tsai T, Chang H, Chao K, Su T, Tsai S. Distant HNF1 site as a master control for the human class I alcohol dehydrogenase gene expression. J Biol Chem. 2006;281:19809-21 pubmed..Taken together, our data indicate that HNF1 binding, at approximately 51 kb upstream, plays a master role in controlling human class I ADH gene expression and may govern alcohol metabolism in the liver. ..