Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ

REFERENCES

• Taub R. 2004. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 5:836–847. https://doi.org/10.1038/nrm1489.
   PubMed Web of Science ®Google Scholar
• Walesky C, Apte U. 2015. Role of hepatocyte nuclear factor 4alpha (HNF4alpha) in cell proliferation and cancer. Gene Expr 16:101–108. https://doi.org/10.3727/105221615X14181438356292.
   PubMed Web of Science ®Google Scholar
• Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. 2001. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21:1393–1403. https://doi.org/10.1128/MCB.21.4.1393-1403.2001.
   PubMed Web of Science ®Google Scholar
• Inoue Y, Hayhurst GP, Inoue J, Mori M, Gonzalez FJ. 2002. Defective ureagenesis in mice carrying a liver-specific disruption of hepatocyte nuclear factor 4alpha (HNF4alpha). HNF4alpha regulates ornithine transcarbamylase in vivo. J Biol Chem 277:25257–25265.
   PubMed Web of Science ®Google Scholar
• Inoue Y, Peters LL, Yim SH, Inoue J, Gonzalez FJ. 2006. Role of hepatocyte nuclear factor 4alpha in control of blood coagulation factor gene expression. J Mol Med 84:334–344. https://doi.org/10.1007/s00109-005-0013-5.
   PubMed Web of Science ®Google Scholar
• Matsuo S, Ogawa M, Muckenthaler MU, Mizui Y, Sasaki S, Fujimura T, Takizawa M, Ariga N, Ozaki H, Sakaguchi M, Gonzalez FJ, Inoue Y. 2015. Hepatocyte nuclear factor 4alpha controls iron metabolism and regulates transferrin receptor 2 in mouse Liver. J Biol Chem 290:30855–30865. https://doi.org/10.1074/jbc.M115.694414.
   PubMed Web of Science ®Google Scholar
• Bonzo JA, Ferry CH, Matsubara T, Kim JH, Gonzalez FJ. 2012. Suppression of hepatocyte proliferation by hepatocyte nuclear factor 4alpha in adult mice. J Biol Chem 287:7345–7356. https://doi.org/10.1074/jbc.M111.334599.
   PubMed Web of Science ®Google Scholar
• Santangelo L, Marchetti A, Cicchini C, Conigliaro A, Conti B, Mancone C, Bonzo JA, Gonzalez FJ, Alonzi T, Amicone L, Tripodi M. 2011. The stable repression of mesenchymal program is required for hepatocyte identity: a novel role for hepatocyte nuclear factor 4alpha. Hepatology 53:2063–2074. https://doi.org/10.1002/hep.24280.
   PubMed Web of Science ®Google Scholar
• Yin C, Wang PQ, Xu WP, Yang Y, Zhang Q, Ning BF, Zhang PP, Zhou WP, Xie WF, Chen WS, Zhang X. 2013. Hepatocyte nuclear factor-4alpha reverses malignancy of hepatocellular carcinoma through regulating miR-134 in the DLK1-DIO3 region. Hepatology 58:1964–1976. https://doi.org/10.1002/hep.26573.
   PubMed Web of Science ®Google Scholar
• Morimoto A, Kannari M, Tsuchida Y, Sasaki S, Saito C, Matsuta T, Maeda T, Akiyama M, Nakamura T, Sakaguchi M, Nameki N, Gonzalez FJ, Inoue Y. 2017. An HNF4alpha-microRNA-194/192 signaling axis maintains hepatic cell function. J Biol Chem 292:10574–10585. https://doi.org/10.1074/jbc.M117.785592.
   PubMed Web of Science ®Google Scholar
• Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, Ogata H, Karin M, Struhl K, Hadzopoulou-Cladaras M, Iliopoulos D. 2011. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell 147:1233–1247. https://doi.org/10.1016/j.cell.2011.10.043.
   PubMed Web of Science ®Google Scholar
• Ning BF, Ding J, Liu J, Yin C, Xu WP, Cong WM, Zhang Q, Chen F, Han T, Deng X, Wang PQ, Jiang CF, Zhang JP, Zhang X, Wang HY, Xie WF. 2014. Hepatocyte nuclear factor 4alpha-nuclear factor-kappaB feedback circuit modulates liver cancer progression. Hepatology 60:1607–1619. https://doi.org/10.1002/hep.27177.
   PubMed Web of Science ®Google Scholar
• Spath GF, Weiss MC. 1997. Hepatocyte nuclear factor 4 expression overcomes repression of the hepatic phenotype in dedifferentiated hepatoma cells. Mol Cell Biol 17:1913–1922. https://doi.org/10.1128/MCB.17.4.1913.
   PubMed Web of Science ®Google Scholar
• Inoue Y, Miyazaki M, Tsuji T, Sakaguchi M, Fukaya K, Huh NH, Namba M. 2001. Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene. Int J Mol Med 8:481–487.
   PubMed Web of Science ®Google Scholar
• Lazarevich NL, Cheremnova OA, Varga EV, Ovchinnikov DA, Kudrjavtseva EI, Morozova OV, Fleishman DI, Engelhardt NV, Duncan SA. 2004. Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology 39:1038–1047. https://doi.org/10.1002/hep.20155.
   PubMed Web of Science ®Google Scholar
• Yin C, Lin Y, Zhang X, Chen YX, Zeng X, Yue HY, Hou JL, Deng X, Zhang JP, Han ZG, Xie WF. 2008. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology 48:1528–1539. https://doi.org/10.1002/hep.22510.
   PubMed Web of Science ®Google Scholar
• Takayama K, Inamura M, Kawabata K, Katayama K, Higuchi M, Tashiro K, Nonaka A, Sakurai F, Hayakawa T, Furue MK, Mizuguchi H. 2012. Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4alpha transduction. Mol Ther 20:127–137. https://doi.org/10.1038/mt.2011.234.
   PubMed Web of Science ®Google Scholar
• Holewa B, Zapp D, Drewes T, Senkel S, Ryffel GU. 1997. HNF4beta, a new gene of the HNF4 family with distinct activation and expression profiles in oogenesis and embryogenesis of Xenopus laevis. Mol Cell Biol 17:687–694. https://doi.org/10.1128/MCB.17.2.687.
   PubMed Web of Science ®Google Scholar
• Drewes T, Senkel S, Holewa B, Ryffel GU. 1996. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol 16:925–931. https://doi.org/10.1128/MCB.16.3.925.
   PubMed Web of Science ®Google Scholar
• Plengvidhya N, Antonellis A, Wogan LT, Poleev A, Borgschulze M, Warram JH, Ryffel GU, Krolewski AS, Doria A. 1999. Hepatocyte nuclear factor-4gamma: cDNA sequence, gene organization, and mutation screening in early-onset autosomal-dominant type 2 diabetes. Diabetes 48:2099–2102. https://doi.org/10.2337/diabetes.48.10.2099.
   PubMed Web of Science ®Google Scholar
• Taraviras S, Mantamadiotis T, Dong-Si T, Mincheva A, Lichter P, Drewes T, Ryffel GU, Monaghan AP, Schutz G. 2000. Primary structure, chromosomal mapping, expression and transcriptional activity of murine hepatocyte nuclear factor 4gamma. Biochim Biophys Acta 1490:21–32. https://doi.org/10.1016/S0167-4781(99)00232-8.
   PubMedGoogle Scholar
• Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA. 2004. Control of pancreas and liver gene expression by HNF transcription factors. Science 303:1378–1381. https://doi.org/10.1126/science.1089769.
   PubMed Web of Science ®Google Scholar
• Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, Rolfe PA, Conboy CM, Gifford DK, Fraenkel E. 2007. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39:730–732. https://doi.org/10.1038/ng2047.
   PubMed Web of Science ®Google Scholar
• Bolotin E, Liao H, Ta TC, Yang C, Hwang-Verslues W, Evans JR, Jiang T, Sladek FM. 2010. Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays. Hepatology 51:642–653. https://doi.org/10.1002/hep.23357.
   PubMed Web of Science ®Google Scholar
• Huang J, Levitsky LL, Rhoads DB. 2009. Novel P2 promoter-derived HNF4alpha isoforms with different N-terminus generated by alternate exon insertion. Exp Cell Res 315:1200–1211. https://doi.org/10.1016/j.yexcr.2009.01.004.
   PubMed Web of Science ®Google Scholar
• Green VJ, Kokkotou E, Ladias JA. 1998. Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. J Biol Chem 273:29950–29957. https://doi.org/10.1074/jbc.273.45.29950.
   PubMed Web of Science ®Google Scholar
• Hadzopoulou-Cladaras M, Kistanova E, Evagelopoulou C, Zeng S, Cladaras C, Ladias JA. 1997. Functional domains of the nuclear receptor hepatocyte nuclear factor 4. J Biol Chem 272:539–550. https://doi.org/10.1074/jbc.272.1.539.
   PubMed Web of Science ®Google Scholar
• Lussier CR, Babeu JP, Auclair BA, Perreault N, Boudreau F. 2008. Hepatocyte nuclear factor-4alpha promotes differentiation of intestinal epithelial cells in a coculture system. Am J Physiol Gastrointest Liver Physiol 294:G418–G428. https://doi.org/10.1152/ajpgi.00418.2007.
   PubMed Web of Science ®Google Scholar
• Stegmann A, Hansen M, Wang Y, Larsen JB, Lund LR, Ritie L, Nicholson JK, Quistorff B, Simon-Assmann P, Troelsen JT, Olsen J. 2006. Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation. Physiol Genomics 27:141–155. https://doi.org/10.1152/physiolgenomics.00314.2005.
   PubMed Web of Science ®Google Scholar
• Pinto M, Robineleon S, Appay MD, Kedinger M, Triadou N, Dussaulx E, Lacroix B, Simonassmann P, Haffen K, Fogh J, Zweibaum A. 1983. Enterocyte-like differentiation and polarization of the human-colon carcinoma cell-line Caco-2 in culture. Biol Cell 47:323–330.
   Web of Science ®Google Scholar
• Boyd M, Bressendorff S, Moller J, Olsen J, Troelsen JT. 2009. Mapping of HNF4alpha target genes in intestinal epithelial cells. BMC Gastroenterol 9:68. https://doi.org/10.1186/1471-230X-9-68.
   PubMed Web of Science ®Google Scholar
• Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, Aburatani H, Naito M, Kodama T, Ihara S, Hamakubo T. 2011. Proteomic analysis of native hepatocyte nuclear factor-4alpha (HNF4alpha) isoforms, phosphorylation status, and interactive cofactors. J Biol Chem 286:674–686. https://doi.org/10.1074/jbc.M110.154732.
   PubMed Web of Science ®Google Scholar
• Sladek FM, Ruse MD, Jr, Nepomuceno L, Huang SM, Stallcup MR. 1999. Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1. Mol Cell Biol 19:6509–6522. https://doi.org/10.1128/MCB.19.10.6509.
   PubMed Web of Science ®Google Scholar
• Vergnes L, Taniguchi T, Omori K, Zakin MM, Ochoa A. 1997. The apolipoprotein A-I/C-III/A-IV gene cluster: ApoC-III and ApoA-IV expression is regulated by two common enhancers. Biochim Biophys Acta 1348:299–310. https://doi.org/10.1016/S0005-2760(97)00071-4.
   PubMedGoogle Scholar
• Sladek FM, Zhong WM, Lai E, Darnell JE, Jr. 1990. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 4:2353–2365. https://doi.org/10.1101/gad.4.12b.2353.
   PubMed Web of Science ®Google Scholar
• Gordon N. 2003. Ornithine transcarbamylase deficiency: a urea cycle defect. Eur J Paediatr Neurol 7:115–121. https://doi.org/10.1016/S1090-3798(03)00040-0.
   PubMed Web of Science ®Google Scholar
• Sousa JF, Nam KT, Petersen CP, Lee HJ, Yang HK, Kim WH, Goldenring JR. 2016. miR-30-HNF4gamma and miR-194-NR2F2 regulatory networks contribute to the upregulation of metaplasia markers in the stomach. Gut 65:914–924. https://doi.org/10.1136/gutjnl-2014-308759.
   PubMed Web of Science ®Google Scholar
• Iyemere VP, Davies NH, Brownlee GG. 1998. The activation function 2 domain of hepatic nuclear factor 4 is regulated by a short C-terminal proline-rich repressor domain. Nucleic Acids Res 26:2098–2104. https://doi.org/10.1093/nar/26.9.2098.
   PubMed Web of Science ®Google Scholar
• Olsen L, Bressendorff S, Troelsen JT, Olsen J. 2005. Differentiation-dependent activation of the human intestinal alkaline phosphatase promoter by HNF-4 in intestinal cells. Am J Physiol Gastrointest Liver Physiol 289:G220–G226. https://doi.org/10.1152/ajpgi.00449.2004.
   PubMed Web of Science ®Google Scholar
• Farkas AE, Hilgarth RS, Capaldo CT, Gerner-Smidt C, Powell DR, Vertino PM, Koval M, Parkos CA, Nusrat A. 2015. HNF4alpha regulates claudin-7 protein expression during intestinal epithelial differentiation. Am J Pathol 185:2206–2218. https://doi.org/10.1016/j.ajpath.2015.04.023.
   PubMed Web of Science ®Google Scholar
• Sauvaget D, Chauffeton V, Citadelle D, Chatelet FP, Cywiner-Golenzer C, Chambaz J, Pincon-Raymond M, Cardot P, Le Beyec J, Ribeiro A. 2002. Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4alpha and gamma isoforms. J Biol Chem 277:34540–34548. https://doi.org/10.1074/jbc.M206074200.
   PubMed Web of Science ®Google Scholar
• Li X, Udager AM, Hu C, Qiao XT, Richards N, Gumucio DL. 2009. Dynamic patterning at the pylorus: formation of an epithelial intestine-stomach boundary in late fetal life. Dev Dyn 238:3205–3217. https://doi.org/10.1002/dvdy.22134.
   PubMed Web of Science ®Google Scholar
• Ahn SH, Shah YM, Inoue J, Morimura K, Kim I, Yim S, Lambert G, Kurotani R, Nagashima K, Gonzalez FJ, Inoue Y. 2008. Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects against inflammatory bowel disease. Inflamm Bowel Dis 14:908–920. https://doi.org/10.1002/ibd.20413.
   PubMed Web of Science ®Google Scholar
• Wu F, Dassopoulos T, Cope L, Maitra A, Brant SR, Harris ML, Bayless TM, Parmigiani G, Chakravarti S. 2007. Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis. Inflamm Bowel Dis 13:807–821. https://doi.org/10.1002/ibd.20110.
   PubMed Web of Science ®Google Scholar
• Bueno-Hernandez N, Sanchez-Munoz F, Barreto-Zuniga R, Dominguez-Lopez A, Yamamoto-Furusho JK. 2011. Expression of HNF4gamma is downregulated in patients with active ulcerative colitis (UC) compared to UC patients in remission and healthy controls. Inflamm Bowel Dis 17:E91. https://doi.org/10.1002/ibd.21753.
   PubMed Web of Science ®Google Scholar
• Li D, Duell EJ, Yu K, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Dong X, Wheeler B, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Mandelson MT, Petersen G, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hoffman Bolton JA, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, et al.. 2012. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. Carcinogenesis 33:1384–1390. https://doi.org/10.1093/carcin/bgs151.
   PubMed Web of Science ®Google Scholar
• Okegawa T, Ushio K, Imai M, Morimoto M, Hara T. 2013. Orphan nuclear receptor HNF4G promotes bladder cancer growth and invasion through the regulation of the hyaluronan synthase 2 gene. Oncogenesis 2:e58. https://doi.org/10.1038/oncsis.2013.25.
   Google Scholar
• Babeu JP, Darsigny M, Lussier CR, Boudreau F. 2009. 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 297:G124–G134. https://doi.org/10.1152/ajpgi.90690.2008.
   PubMed Web of Science ®Google Scholar
• Moore BD, Khurana SS, Huh WJ, Mills JC. 2016. Hepatocyte nuclear factor 4alpha is required for cell differentiation and homeostasis in the adult mouse gastric epithelium. Am J Physiol Gastrointest Liver Physiol 311:G267–G275. https://doi.org/10.1152/ajpgi.00195.2016.
   PubMed Web of Science ®Google Scholar
• Xu L, Hui L, Wang S, Gong J, Jin Y, Wang Y, Ji Y, Wu X, Han Z, Hu G. 2001. Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma. Cancer Res 61:3176–3181.
   PubMed Web of Science ®Google Scholar
• Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, Kaestner KH, Rossi JM, Zaret KS, Duncan SA. 2003. Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 34:292–296. https://doi.org/10.1038/ng1175.
   PubMed Web of Science ®Google Scholar
• Sekiya S, Suzuki A. 2011. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475:390–393. https://doi.org/10.1038/nature10263.
   PubMed Web of Science ®Google Scholar
• Schreiber E, Matthias P, Muller MM, Schaffner W. 1989. Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Res 17:6419. https://doi.org/10.1093/nar/17.15.6419.
   PubMed Web of Science ®Google Scholar
• Kimura A, Nishiyori A, Murakami T, Tsukamoto T, Hata S, Osumi T, Okamura R, Mori M, Takiguchi M. 1993. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). J Biol Chem 268:11125–11133.
   PubMed Web of Science ®Google Scholar
• Sakaguchi M, Watanabe M, Kinoshita R, Kaku H, Ueki H, Futami J, Murata H, Inoue Y, Li SA, Huang P, Putranto EW, Ruma IM, Nasu Y, Kumon H, Huh NH. 2014. Dramatic increase in expression of a transgene by insertion of promoters downstream of the cargo gene. Mol Biotechnol 56:621–630. https://doi.org/10.1007/s12033-014-9738-0.
   PubMed Web of Science ®Google Scholar
• Inoue Y, Yu AM, Yim SH, Ma X, Krausz KW, Inoue J, Xiang CC, Brownstein MJ, Eggertsen G, Bjorkhem I, Gonzalez FJ. 2006. Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4alpha. J Lipid Res 47:215–227. https://doi.org/10.1194/jlr.M500430-JLR200.
   PubMed Web of Science ®Google Scholar