Mechanisms of mutual functional interactions between HNF-4α and HNF-1α revealed by mutations that cause maturity onset diabetes of the young

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 290, Issue 3, 2006, Pages

  Rowley, Christopher W ^a   Staloch, Lora J ^a   Divine, Joyce K ^a   McCaul, Sean P ^a   Simon, Theodore C ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Hepatic nuclear factor 1; Hepatic nuclear factor 4; Transcription factor

Indexed keywords

HEPATOCYTE NUCLEAR FACTOR 1ALPHA; HEPATOCYTE NUCLEAR FACTOR 4; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; FABP1 PROTEIN, HUMAN; FATTY ACID BINDING PROTEIN; HNF4A PROTEIN, HUMAN;

ARTICLE; BINDING SITE; GENE ACTIVATION; HUMAN; HUMAN CELL; LIPID METABOLISM; MATURITY ONSET DIABETES MELLITUS; MISSENSE MUTATION; MUTATION; PHENOTYPE; PRECIPITATION; PRIORITY JOURNAL; PROMOTER REGION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; WILD TYPE; CELL STRAIN CACO 2; GENETICS; HELA CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOPHYSIOLOGY; PHYSIOLOGY; TRANSGENE;

CACO-2 CELLS; DIABETES MELLITUS, TYPE 2; FATTY ACID-BINDING PROTEINS; HELA CELLS; HEPATOCYTE NUCLEAR FACTOR 1-ALPHA; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; MUTATION, MISSENSE; PROMOTER REGIONS (GENETICS); TRANSGENES;

EID: 33644983700     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00431.2005     Document Type: Article

References (56)

1. Akiyama TE, Ward JM, and Gonzalez FJ. Regulation of the liver fatty acid-binding protein gene by hepatocyte nuclear factor 1α (HNF-1α). Alterations in fatty acid homeostasis in HNF-1α-deficient mice. J Biol Chem 275: 27117-27122, 2000.
2. Bach I, Mattei MG, Cereghini S, and Yaniv M. Two members of an HNF-1 homeoprotein family are expressed in human liver. Nucleic Acids Res 19: 3553-3559, 1991.
3. Bass NM, Manning JA, Ockner RK, Gordon JI, Seetharam S, and Alpers DH. Regulation of the biosynthesis of two distinct fatty acid-binding proteins in rat liver and intestine. Influences of sex difference and of clofibrate. J Biol Chem 260: 1432-1436, 1985.
4. Bjorkhaug L, Sagen JV, Thorsby P, Sovik O, Molven A, and Njolstad PR. Hepatocyte nuclear factor-1α gene mutations and diabetes in Norway. J Clin Endocrinol Metab 88: 920-931, 2003.
5. Briancon N, Bailly A, Clotman F, Jacquemin P, Lemaigre FP, and Weiss MC. Expression of the α7 isoform of HNF4 is activated by HNF6/OC-2 and HNF1, and repressed by HNF4α1 in the liver. J Biol Chem 24: 33398-33408, 2004.
6. Bulman MP, Ellard S, and Hattersley AT. R127W in HNF4α is a loss-of-function mutation causing maturity-onset diabetes of the young (MODY) in a UK Caucasian family. Diabetologia 43: 1203, 2000.
7. Cao H, Shorey S, Robinson J, Metzger DL, Stewart L, Cummings E, and Hegele RA. GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY). Hum Mutat 20: 478-479, 2002.
8. Divine J, Staloch L, Haveri H, Jacobsen C, Wilson D, Heikinheimo M, and Simon T. GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene in concert with HNF 1α. Am J Physiol Gastrointest Liver Physiol 287: G1086-G1099, 2004.
9. Divine JK, McCaul SP, and Simon TC. HNF-1α and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity. Am J Physiol Gastrointest Liver Physiol 285: G62-G72, 2003.
10. Dogra SC and May BK. Liver-enriched transcription factors, HNF-1, HNF-3, and C/EBP are major contributors to the strong activity of the chicken CYP2H1 promoter in chick embryo hepatocytes. DNA Cell Biol 16: 1407-1418, 1997.
11. Eeckhoute J, Formstecher P, and Laine B. Hepatocyte nuclear factor 4α enhances the hepatocyte nuclear factor 1α-mediated activation of transcription. Nucleic Acids Res 32: 2586-2593, 2004.
12. Eeckhoute J, Formstecher P, and Laine B. Maturity-onset diabetes of the young Type 1 (MODY1)-associated mutations R154X and E276Q in hepatocyte nuclear factor 4α (HNF4α) gene impair recruitment of p300, a key transcriptional co-activator. Mol Endocrinol 15: 1200-1210, 2001.
13. Ellard S. Hepatocyte nuclear factor 1α (HNF-1α) mutations in maturity-onset diabetes of the young. Hum Mutat 16: 377-385, 2000.
14. Furuta H, Iwasaki N, Oda N, Hinokio Y, Horikawa Y, Yamagata K, Yano N, Sugahiro J, Ogata M, Ohgawara H, Omori Y, Iwamoto Y, and Bell GI. Organization and partial sequence of the hepatocyte nuclear factor-4α/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. Diabetes 46: 1652-1657, 1997.
15. Gregori C, Porteu A, Lopez S, Kahn A, and Pichard AL. Characterization of the aldolase B intronic enhancer. J Biol Chem 273: 25237-25243, 1998.
16. Hansen SK, Parrizas M, Jensen ML, Pruhova S, Ek J, Boj SF, Johansen A, Maestro MA, Rivera F, Eiberg H, Andel M, Lebl J, Pedersen O, Ferrer J, and Hansen T. Genetic evidence that HNF-1α-dependent transcriptional control of HNF-4α is essential for human pancreatic β-cell function. J Clin Invest 110: 827-833, 2002.
17. Hatzis P and Talianidis I. Regulatory mechanisms controlling human hepatocyte nuclear factor 4α gene expression. Mol Cell Biol 21: 7320-7330, 2001.
18. Hayhurst GP, Lee YH, Lambert G, Ward JM, and Gonzalez FJ. Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21: 1393-1403, 2001.
19. 1-antitrypsin gene expression in human intestinal epithelial cell line Caco-2 by HNF-1α and HNF-4. Am J Physiol Gastrointest Liver Physiol 276: G1181-G1194, 1999.
20. Iwasaki N, Oda N, Ogata M, Hara M, Hinokio Y, Oda Y, Yamagata K, Kanematsu S, Ohgawara H, Omori Y, and Bell GI. Mutations in the hepatocyte nuclear factor-1α/MODY3 gene in Japanese subjects with early- and late-onset NIDDM. Diabetes 46: 1504-1508, 1997.
21. Jiang G, Lee U, and Sladek FM. Proposed mechanism for the stabilization of nuclear receptor DNA binding via protein dimerization. Mol Cell Biol 17: 6546-6554, 1997.
22. Kritis AA, Ktistaki E, Barda D, Zannis VI, and Talianidis I. An indirect negative autoregulatory mechanism involved in hepatocyte nuclear factor-1 gene expression. Nucleic Acids Res 21: 5882-5889, 1993.
23. Ktistaki E and Talianidis I. Modulation of hepatic gene expression by hepatocyte nuclear factor 1. Science 277: 109-112, 1997.
24. Ladias JA, Hadzopoulou-Cladaras M, Kardassis D, Cardot P, Cheng J, Zannis V, and Cladaras C. Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3. J Biol Chem 267: 15849-15860, 1992.
25. Lausen J, Thomas H, Lemm I, Bulman M, Borgschulze M, Lingott A, Hattersley AT, and Ryffel GU. Naturally occurring mutations in the human HNF-4α gene impair the function of the transcription factor to a varying degree. Nucleic Acids Res 28: 430-437, 2000.
26. Lavrentiadou SN, Hadzopoulou-Cladaras M, Kardassis D, and Zannis VI. Binding specificity and modulation of the human ApoCIII promoter activity by heterodimers of ligand-dependent nuclear receptors. Biochemistry 38: 964-975, 1999.
27. Matsumura K, Saito T, Takahashi Y, Ozeki T, Kiyotani K, Fujieda M, Yamazaki H, Kunitoh H, and Kamataki T. Identification of a novel polymorphic enhancer of the human CYP3A4 gene. Mol Pharmacol 65: 326-334, 2004.
28. Mendel DB, Hansen LP, Graves MK, Conley PB, and Crabtree GR. HNF-1α and HNF-1β (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev 5: 1042-1056, 1991.
29. Navas MA, Munoz-Elias EJ, Kim J, Shih D, and Stoffel M. Functional characterization of the MODY1 gene mutations HNF4 (R127W), HNF4 (V255M), and HNF4 (E276Q). Diabetes 48: 1459-1465, 1999.
30. Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, and Young RA. Control of pancreas and liver gene expression by HNF transcription factors. Science 303: 1378-1381, 2004.
31. Owen K and Hattersley AT. Maturity-onset diabetes of the young: from clinical description to molecular genetic characterization. Best Pract Res Clin Endocrinol Metab 15: 309-323, 2001.
32. Oxombre B, Kouach M, Moerman E, Formstecher P, and Laine B. The G115S mutation associated with maturity-onset diabetes of the young impairs hepatocyte nuclear factor 4α activities and introduces a PKA phosphorylation site in its DNA-binding domain. Biochem J 383: 573-580, 2004.
33. Oxombre B, Moerman E, Eeckhoute J, Formstecher P, and Laine B. Mutations in hepatocyte nuclear factor 4α (HNF4α) gene associated with diabetes result in greater loss of HNF4α function in pancreatic β-cells than in nonpancreatic β-cells and in reduced activation of the apolipoprotein CIII promoter in hepatic cells. J Mol Med 80: 423-430, 2002.
34. Ozeki T, Takahashi Y, Kume T, Nakayama K, Yokoi T, Nunoya K, Hara A, and Kamataki T. Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4α/γ and HNF-1α. Biochem J 355: 537-544, 2001.
35. Ozeki T, Takahashi Y, Nakayama K, Funayama M, Nagashima K, Kodama T, and Kamataki T. Hepatocyte nuclear factor-4α/γ and hepatocyte nuclear factor-1α as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers. Pharmacogenetics 13: 49-53, 2003.
36. Pearson ER, Pruhova S, Tack CJ, Johansen A, Castleden HA, Lumb PJ, Wierzbicki AS, Clark PM, Lebl J, Pedersen O, Ellard S, Hansen T, and Hattersley AT. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4α mutations in a large European collection. Diabetologia 48: 878-885, 2005.
37. Poirier H, Braissant O, Niot I, Wahli W, and Besnard P. 9-Cis-retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene. FEBS Lett 412: 480-484, 1997.
38. Richter S, Shih DQ, Pearson ER, Wolfrum C, Fajans SS, Hattersley AT, and Stoffel M. Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-1α: Haploinsufficiency is associated with reduced serum apolipoprotein M levels. Diabetes 52: 2989-2995, 2003.
39. Rubins NE, Friedman JR, Le PP, Zhang L, Brestelli J, and Kaestner KH. Transcriptional networks in the liver: hepatocyte nuclear factor 6 function is largely independent of Foxa2. Mol Cell Biol 25: 7069-7077, 2005.
40. Ryffel GU. 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 27: 11-29, 2001.
41. Schug J and Overton GC. TESS: Transcription Element Search Software on the WWW Computational Biology and Informatics Laboratory, University of Pennsylvania School of Medicine. [Online: http://www.cbil.upenn.edu/tess.2004.]
42. Sheena V, Hertz R, Nousbeck J, Berman I, Magenheim J, and Bar-Tana J. Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4α. J Lipid Res 46: 328-341, 2005.
43. Shih DQ, Dansky HM, Fleisher M, Assmann G, Fajans SS, and Stoffel M. Genotype/phenotype relationships in HNF-4α MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein (a), and triglyceride levels. Diabetes 49: 832-837, 2000.
44. Simon TC, Roth KA, and Gordon JI. Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J Biol Chem 268: 18345-18358, 1993.
45. Sladek FM, Zhong WM, Lai E, and Darnell JE Jr. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 4: 2353-2365, 1990.
46. Soutoglou E, Viollet B, Vaxillaire M, Yaniv M, Pontoglio M, and Talianidis I. Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity. EMBO J 20: 1984-1992, 2001.
47. Stratman J, Barnes W, and Simon TC. Universal PCR genotyping assay that achieves single copy sensitivity with any primer pair. Transgenic Res 12: 521-522, 2003.
48. Suaud L, Hemimou Y, Formstecher P, and Laine B. Functional study of the E276Q mutant hepatocyte nuclear factor-4α found in type 1 maturity-onset diabetes of the young: impaired synergy with chicken ovalbumin upstream promoter transcription factor II on the hepatocyte nuclear factor-1 promoter. Diabetes 48: 1162-1167, 1999.
49. Sweetser DA, Birkenmeier EH, Hoppe PC, McKeel DW, and Gordon JI. Mechanisms underlying generation of gradients in gene expression within the intestine: an analysis using transgenic mice containing fatty acid binding protein-human growth hormone fusion genes. Genes Dev 2: 1318-1332, 1988.
50. Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott-Frieg A, Tack CJ, Ellard S, Ryffel GU, and Hattersley AT. A distant upstream promoter of the HNF-4α gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 10: 2089-2097, 2001.
51. Torres-Padilla ME, Fougere-Deschatrette C, and Weiss MC. Expression of HNF4α isoforms in mouse liver development is regulated by sequential promoter usage and constitutive 3′ end splicing. Mech Dev 109: 183-193, 2001.
52. Vaxillaire M, Abderrahmani A, Boutin P, Bailleul B, Froguel P, Yaniv M, and Pontoglio M. Anatomy of a homeoprotein revealed by the analysis of human MODY3 mutations. J Biol Chem 274: 35639-35646, 1999.
53. Wingender E, Chen X, Fricke E, Geffers R, Hehl R, Liebich I, Krull M, Matys V, Michael H, Ohnhäuser R, MP, Schacherer F, Thiele S, and Urbach S. The TRANSFAC system on gene expression regulation. Nucleic Acids Res 29: 281-283, 2001.
54. Yang Q, Yamagata K, Yamamoto K, Cao Y, Miyagawa J, Fukamizu A, Hanafusa T, and Matsuzawa Y. R127W-HNF-4α is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1. Diabetologia 43: 520-524, 2000.
55. Yang Q, Yamagata K, Yamamoto K, Miyagawa J, Takeda J, Iwasaki N, Iwahashi H, Yoshiuchi I, Namba M, Miyazaki J, Hanafusa T, and Matsuzawa Y. Structure/function studies of hepatocyte nuclear factor-1α, a diabetes-associated transcription factor. Biochem Biophys Res Commun 266: 196-202, 1999.
56. Zhu Q, Yamagata K, Miura A, Shihara N, Horikawa Y, Takeda J, Miyagawa J, and Matsuzawa Y. T130I mutation in HNF-4α gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. Diabetologia 46: 567-573, 2003.