Transcriptional factors mediating retinoic acid signals in the control of energy metabolism

International Journal of Molecular Sciences

Volumn 16, Issue 6, 2015, Pages 14210-14244

  Zhang, Rui ^a   Wang, Yueqiao ^b   Li, Rui ^b   Chen, Guoxun ^c  

^a Wuhan Food and Drug Administration   (China)

^b WUHAN UNIVERSITY   (China)

^c UNIVERSITY OF TENNESSEE   (United States)

Author keywords

Chicken ovalbumin upstream Transcription factor II; Hepatic nuclear factor 4 ; Metabolism; Peroxisome proliferator activated receptor ; Retinoic acid; Retinoic acid receptor; Retinoid X receptor; Vitamin A

Indexed keywords

CELL NUCLEUS RECEPTOR; CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR 2; HEPATOCYTE NUCLEAR FACTOR 4; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); RETINOIC ACID; TRANSCRIPTION FACTOR; ANTINEOPLASTIC AGENT; RETINOIC ACID RECEPTOR;

ADIPOGENESIS; ANIMAL CELL; BINDING SITE; CHROMATIN IMMUNOPRECIPITATION; DNA BINDING; DOWN REGULATION; DRUG UPTAKE; ENERGY METABOLISM; GENE EXPRESSION; GENE SEQUENCE; NONHUMAN; PHYSIOLOGICAL PROCESS; PROTEIN EXPRESSION; REVIEW; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; ANIMAL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM;

ANIMALS; ANTINEOPLASTIC AGENTS; ENERGY METABOLISM; GENE EXPRESSION REGULATION; HUMANS; RECEPTORS, RETINOIC ACID; TRANSCRIPTION FACTORS; TRETINOIN;

EID: 84934904904     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms160614210     Document Type: Review

References (255)

1. Zhao, S.; Li, R.; Li, Y.; Chen, W.; Zhang, Y.; Chen, G. Roles of vitamin A status and retinoids in glucose and fatty acid metabolism. Biochem. Cell Biol. 2012, 90, 142–152.
2. Berry, D.C.; Levi, L.; Noy, N. Holo-retinol-binding protein and its receptor STRA6 drive oncogenic transformation. Cancer Res. 2014, 74, 6341–6351.
3. Di Masi, A.; Leboffe, L.; de Marinis, E.; Pagano, F.; Cicconi, L.; Rochette-Egly, C.; Lo-Coco, F.; Ascenzi, P.; Nervi, C. Retinoic acid receptors: From molecular mechanisms to cancer therapy. Mol. Asp. Med. 2015, 41, 1–115.
4. Chen, W.; Howell, M.L.; Li, Y.; Li, R.; Chen, G. Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes. PLoS ONE 2014, 9, e100868.
5. Olson, J.A. Needs and sources of carotenoids and vitamin A. Nutr. Rev. 1994, 52, S67–S73.
6. Harrison, E.H. Enzymes catalyzing the hydrolysis of retinyl esters. Biochim. Biophys. Acta 1993, 1170, 99–108.
7. Devery, J.; Milborrow, B.V. β-Carotene-15,15′-dioxygenase (EC 1.13.11.21) isolation reaction mechanism and an improved assay procedure. Br. J. Nutr. 1994, 72, 397–414.
8. Wang, X.D.; Krinsky, N.I.; Tang, G.W.; Russell, R.M. Retinoic acid can be produced from excentric cleavage of β-carotene in human intestinal mucosa. Arch. Biochem. Biophys. 1992, 293, 298–304.
9. Helgerud, P.; Petersen, L.B.; Norum, K.R. Retinol esterification by microsomes from the mucosa of human small intestine. Evidence for acyl-Coenzyme A retinol acyltransferase activity. J. Clin. Investig. 1983, 71, 747–753.
10. MacDonald, P.N.; Ong, D.E. Evidence for a lecithin-retinol acyltransferase activity in the rat small intestine. J. Biol. Chem. 1988, 263, 12478–12482.
11. Blomhoff, R.; Green, M.H.; Green, J.B.; Berg, T.; Norum, K.R. Vitamin A metabolism: New perspectives on absorption, transport, and storage. Physiol. Rev. 1991, 71, 951–990.
12. Wongsiriroj, N.; Piantedosi, R.; Palczewski, K.; Goldberg, I.J.; Johnston, T.P.; Li, E.; Blaner, W.S. The molecular basis of retinoid absorption: A genetic dissection. J. Biol. Chem. 2008, 283, 13510–13519.
13. Ruiz, A.; Winston, A.; Lim, Y.H.; Gilbert, B.A.; Rando, R.R.; Bok, D. Molecular and biochemical characterization of lecithin retinol acyltransferase. J. Biol. Chem. 1999, 274, 3834–3841.
14. Shih, M.Y.; Kane, M.A.; Zhou, P.; Yen, C.L.; Streeper, R.S.; Napoli, J.L.; Farese, R.V. Retinol esterification by DGAT1 is essential for retinoid homeostasis in murine skin. J. Biol. Chem. 2009, 284, 4292–4299.
15. Orland, M.D.; Anwar, K.; Cromley, D.; Chu, C.H.; Chen, L.; Billheimer, J.T.; Hussain, M.M.; Cheng, D. Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: Diacylglycerol acyltransferase 1. Biochim. Biophys. Acta 2005, 1737, 76–82.
16. Harrison, E.H. Mechanisms of digestion and absorption of dietary vitamin A. Annu. Rev. Nutr. 2005, 25, 87–103.
17. During, A.; Harrison, E.H. Mechanisms of provitamin A (carotenoid) and vitamin A (retinol) transport into and out of intestinal Caco-2 cells. J. Lipid Res. 2007, 48, 2283–2294.
18. Goodman, D.W.; Huang, H.S.; Shiratori, T. Tissue distribution and metabolism of newly absorbed vitamin A in the rat. J. Lipid Res. 1965, 6, 390–396.
19. Lobo, G.P.; Amengual, J.; Palczewski, G.; Babino, D.; von Lintig, J. Mammalian carotenoid-oxygenases: Key players for carotenoid function and homeostasis. Biochim. Biophys. Acta 2012, 1821, 78–87.
20. Harrison, E.H.; Gad, M.Z.; Ross, A.C. Hepatic uptake and metabolism of chylomicron retinyl esters: Probable role of plasma membrane/endosomal retinyl ester hydrolases. J. Lipid Res. 1995, 36, 1498–1506.
21. Raghu, P.; Sivakumar, B. Interactions amongst plasma retinol-binding protein, transthyretin and their ligands: Implications in vitamin A homeostasis and transthyretin amyloidosis. Biochim. Biophys. Acta 2004, 1703, 1–9.
22. Noy, N. Retinoid-binding proteins: Mediators of retinoid action. Biochem. J. 2000, 348, 481–495.
23. Blomhoff, R.; Blomhoff, H.K. Overview of retinoid metabolism and function. J. Neurobiol. 2006, 66, 606–630.
24. Blomhoff, R. Transport and metabolism of vitamin A. Nutr. Rev. 1994, 52, S13–S23.
25. Batten, M.L.; Imanishi, Y.; Maeda, T.; Tu, D.C.; Moise, A.R.; Bronson, D.; Possin, D.; van Gelder, R.N.; Baehr, W.; Palczewski, K. Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver. J. Biol. Chem. 2004, 279, 10422–10432.
26. Kawaguchi, R.; Yu, J.; Honda, J.; Hu, J.; Whitelegge, J.; Ping, P.; Wiita, P.; Bok, D.; Sun, H. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 2007, 315, 820–825.
27. Blaner, W.S. STRA6, a cell-surface receptor for retinol-binding protein: The plot thickens. Cell Metab. 2007, 5, 164–166.
28. Isken, A.; Golczak, M.; Oberhauser, V.; Hunzelmann, S.; Driever, W.; Imanishi, Y.; Palczewski, K.; von Lintig, J. RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew–Wood syndrome. Cell Metab. 2008, 7, 258–268.
29. Berry, D.C.; Noy, N. Signaling by vitamin A and retinol-binding protein in regulation of insulin responses and lipid homeostasis. Biochim. Biophys. Acta 2012, 1821, 168–176.
30. Berry, D.C.; Jin, H.; Majumdar, A.; Noy, N. Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses. Proc. Natl. Acad. Sci. USA 2011, 108, 4340–4345.
31. Zemany, L.; Kraus, B.J.; Norseen, J.; Saito, T.; Peroni, O.D.; Johnson, R.L.; Kahn, B.B. Downregulation of STRA6 in adipocytes and adipose stromovascular fraction in obesity and effects of adipocyte-specific STRA6 knockdown in vivo. Mol. Cell. Biol. 2014, 34, 1170–1186.
32. Berry, D.C.; Jacobs, H.; Marwarha, G.; Gely-Pernot, A.; O’Byrne, S.M.; DeSantis, D.; Klopfenstein, M.; Feret, B.; Dennefeld, C.; Blaner, W.S. et al. The STRA6 receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining vitamin A homeostasis in tissues other than the eye. J. Biol. Chem. 2013, 288, 24528–24539.
33. Pares, X.; Farres, J.; Kedishvili, N.; Duester, G. Medium- and short-chain dehydrogenase/reductase gene and protein families: Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism. Cell. Mol. Life Sci. 2008, 65, 3936–3949.
34. Persson, B.; Hedlund, J.; Jornvall, H. Medium- and short-chain dehydrogenase/reductase gene and protein families: The MDR superfamily. Cell. Mol. Life Sci. 2008, 65, 3879–3894.
35. Kavanagh, K.L.; Jornvall, H.; Persson, B.; Oppermann, U. Medium- and short-chain dehydrogenase/reductase gene and protein families: The SDR superfamily: Functional and structural diversity within a family of metabolic and regulatory enzymes. Cell. Mol. Life Sci. 2008, 65, 3895–3906.
36. Duester, G. Retinoic acid synthesis and signaling during early organogenesis. Cell 2008, 134, 921–931.
37. Molotkov, A.; Duester, G. Genetic evidence that retinaldehyde dehydrogenase Raldh1 (Aldh1a1) functions downstream of alcohol dehydrogenase Adh1 in metabolism of retinol to retinoic acid. J. Biol. Chem. 2003, 278, 36085–36090.
38. Elizondo, G.; Corchero, J.; Sterneck, E.; Gonzalez, F.J. Feedback inhibition of the retinaldehyde dehydrogenase gene ALDH1 by retinoic acid through retinoic acid receptor α and CCAAT/ enhancer-binding protein β. J. Biol. Chem. 2000, 275, 39747–39753.
39. Elizondo, G.; Medina-Diaz, I.M.; Cruz, R.; Gonzalez, F.J.; Vega, L. Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153-C/EBPβ interaction. Biochem. Pharmacol. 2009, 77, 248–257.
40. Sandell, L.L.; Lynn, M.L.; Inman, K.E.; McDowell, W.; Trainor, P.A. RDH10 oxidation of vitamin A is a critical control step in synthesis of retinoic acid during mouse embryogenesis. PLoS ONE 2012, 7, e30698.
41. Reijntjes, S.; Gale, E.; Maden, M. Generating gradients of retinoic acid in the chick embryo: Cyp26C1 expression and a comparative analysis of the Cyp26 enzymes. Dev. Dyn. 2004, 230, 509–517.
42. Noy, N. The one-two punch: Retinoic acid suppresses obesity both by promoting energy expenditure and by inhibiting adipogenesis. Adipocyte 2013, 2, 184–187.
43. Sucov, H.M.; Murakami, K.K.; Evans, R.M. Characterization of an autoregulated response element in the mouse retinoic acid receptor type β gene. Proc. Natl. Acad. Sci. USA 1990, 87, 5392–5396.
44. Hoffmann, B.; Lehmann, J.M.; Zhang, X.K.; Hermann, T.; Husmann, M.; Graupner, G.; Pfahl, M. A retinoic acid receptor-specific element controls the retinoic acid receptor-β promoter. Mol. Endocrinol. 1990, 4, 1727–1736.
45. De The, H.; Vivanco-Ruiz, M.M.; Tiollais, P.; Stunnenberg, H.; Dejean, A. Identification of a retinoic acid responsive element in the retinoic acid receptor β gene. Nature 1990, 343, 177–180.
46. Mahony, S.; Mazzoni, E.O.; McCuine, S.; Young, R.A.; Wichterle, H.; Gifford, D.K. Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis. Genome Biol. 2011, 12, R2.
47. Balmer, J.E.; Blomhoff, R. A robust characterization of retinoic acid response elements based on a comparison of sites in three species. J. Steroid Biochem. Mol. Biol. 2005, 96, 347–354.
48. Moutier, E.; Ye, T.; Choukrallah, M.A.; Urban, S.; Osz, J.; Chatagnon, A.; Delacroix, L.; Langer, D.; Rochel, N.; Moras, D. et al. Retinoic acid receptors recognize the mouse genome through binding elements with diverse spacing and topology. J. Biol. Chem. 2012, 287, 26328–26341.
49. Mader, S.; Chen, J.Y.; Chen, Z.; White, J.; Chambon, P.; Gronemeyer, H. The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains. EMBO J. 1993, 12, 5029–5041.
50. Perlmann, T.; Rangarajan, P.N.; Umesono, K.; Evans, R.M. Determinants for selective RAR and TR recognition of direct repeat HREs. Genes Dev. 1993, 7, 1411–1422.
51. Kurokawa, R.; DiRenzo, J.; Boehm, M.; Sugarman, J.; Gloss, B.; Rosenfeld, M.G.; Heyman, R.A.; Glass, C.K. Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature 1994, 371, 528–531.
52. Vasios, G.; Mader, S.; Gold, J.D.; Leid, M.; Lutz, Y.; Gaub, M.P.; Chambon, P.; Gudas, L. The late retinoic acid induction of laminin B1 gene transcription involves RAR binding to the responsive element. EMBO J. 1991, 10, 1149–1158.
53. Vasios, G.W.; Gold, J.D.; Petkovich, M.; Chambon, P.; Gudas, L.J. A retinoic acid-responsive element is present in the 5′ flanking region of the laminin B1 gene. Proc. Natl. Acad. Sci. USA 1989, 86, 9099–9103.
54. Li, R.; Zhang, R.; Li, Y.; Zhu, B.; Chen, W.; Zhang, Y.; Chen, G. A RARE of hepatic Gck promoter interacts with RARα, HNF4α and COUP-TFII that affect retinoic acid- and insulin-induced Gck expression. J. Nutr. Biochem. 2014, 25, 964–976.
55. Bastien, J.; Rochette-Egly, C. Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 2004, 328, 1–16.
56. Durand, B.; Saunders, M.; Leroy, P.; Leid, M.; Chambon, P. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell 1992, 71, 73–85.
57. Brade, T.; Kumar, S.; Cunningham, T.J.; Chatzi, C.; Zhao, X.; Cavallero, S.; Li, P.; Sucov, H.M.; Ruiz-Lozano, P.; Duester, G. Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development 2011, 138, 139–148.
58. Loudig, O.; Babichuk, C.; White, J.; Abu-Abed, S.; Mueller, C.; Petkovich, M. Cytochrome P450RAI(CYP26) promoter: A distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism. Mol. Endocrinol. 2000, 14, 1483–1497.
59. Lee, C.H.; Wei, L.N. Characterization of an inverted repeat with a zero spacer (IR0)-type retinoic acid response element from the mouse nuclear orphan receptor TR2–11 gene. Biochemistry 1999, 38, 8820–8825.
60. Chen, G. Roles of vitamin A metabolism in the development of hepatic insulin resistance. ISRN Hepatol. 2013, 2013, 1–21.
61. Germain, P.; Chambon, P.; Eichele, G.; Evans, R.M.; Lazar, M.A.; Leid, M.; de Lera, A.R.; Lotan, R.; Mangelsdorf, D.J.; Gronemeyer, H. International union of pharmacology. LX. Retinoic acid receptors. Pharmacol. Rev. 2006, 58, 712–725.
62. Schug, T.T.; Berry, D.C.; Shaw, N.S.; Travis, S.N.; Noy, N. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell 2007, 129, 723–733.
63. Chambon, P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996, 10, 940–954.
64. Berry, D.C.; Noy, N. Is PPARβ/δ a retinoid receptor? PPAR Res. 2007, 2007, 73256.
65. Stehlin-Gaon, C.; Willmann, D.; Zeyer, D.; Sanglier, S.; Van Dorsselaer, A.; Renaud, J.P.; Moras, D.; Schule, R. All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR β. Nat. Struct. Biol. 2003, 10, 820–825.
66. Kruse, S.W.; Suino-Powell, K.; Zhou, X.E.; Kretschman, J.E.; Reynolds, R.; Vonrhein, C.; Xu, Y.; Wang, L.; Tsai, S.Y.; Tsai, M.J. et al. Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. PLoS Biol. 2008, 6, e227.
67. Bookout, A.L.; Jeong, Y.; Downes, M.; Yu, R.T.; Evans, R.M.; Mangelsdorf, D.J. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 2006, 126, 789–799.
68. Delfosse, V.; Maire, A.L.; Balaguer, P.; Bourguet, W. A structural perspective on nuclear receptors as targets of environmental compounds. Acta Pharmacol. Sin. 2014, doi:10.1038/aps.2014.133.
69. Gronemeyer, H.; Gustafsson, J.A.; Laudet, V. Principles for modulation of the nuclear receptor superfamily. Nat. Rev. Drug Discov. 2004, 3, 950–964.
70. Chawla, A.; Repa, J.J.; Evans, R.M.; Mangelsdorf, D.J. Nuclear receptors and lipid physiology: Opening the X-files. Science 2001, 294, 1866–1870.
71. Mangelsdorf, D.J.; Evans, R.M. The RXR heterodimers and orphan receptors. Cell 1995, 83, 841–850.
72. Glass, C.K.; Rosenfeld, M.G. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000, 14, 121–141.
73. Durand, B.; Saunders, M.; Gaudon, C.; Roy, B.; Losson, R.; Chambon, P. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: Presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity. EMBO J. 1994, 13, 5370–5382.
74. Mangelsdorf, D.J.; Thummel, C.; Beato, M.; Herrlich, P.; Schutz, G.; Umesono, K.; Blumberg, B.; Kastner, P.; Mark, M.; Chambon, P. et al. The nuclear receptor superfamily: The second decade. Cell 1995, 83, 835–839.
75. Moras, D.; Gronemeyer, H. The nuclear receptor ligand-binding domain: Structure and function. Curr. Opin. Cell Biol. 1998, 10, 384–391.
76. Aranda, A.; Pascual, A. Nuclear hormone receptors and gene expression. Physiol. Rev. 2001, 81, 1269–1304.
77. Gadaleta, R.M.; Magnani, L. Nuclear receptors and chromatin: An inducible couple. J. Mol. Endocrinol. 2014, 52, R137–R149.
78. Papacleovoulou, G.; Abu-Hayyeh, S.; Williamson, C. Nuclear receptor-driven alterations in bile acid and lipid metabolic pathways during gestation. Biochim. Biophys. Acta 2011, 1812, 879-887.
79. McKenna, N.J.; Xu, J.; Nawaz, Z.; Tsai, S.Y.; Tsai, M.J.; O’Malley, B.W. Nuclear receptor coactivators: Multiple enzymes, multiple complexes, multiple functions. J. Steroid Biochem. Mol. Biol 1999, 69, 3-12.
80. Hermanson, O.; Glass, C.K.; Rosenfeld, M.G. Nuclear receptor coregulators: Multiple modes of modification. Trends Endocrinol. Metab. 2002, 13, 55-60.
81. Evans, R.M. The nuclear receptor superfamily: A rosetta stone for physiology. Mol Endocrinol 2005, 19, 1429-1438.
82. Heyman, R.A.; Mangelsdorf, D.J.; Dyck, J.A.; Stein, R.B.; Eichele, G.; Evans, R.M.; Thaller, C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992, 68, 397-406.
83. Levin, A.A.; Sturzenbecker, L.J.; Kazmer, S.; Bosakowski, T.; Huselton, C.; Allenby, G.; Speck, J.; Kratzeisen, C.; Rosenberger, M.; Lovey, A. et al 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR a. Nature 1992, 355, 359-361.
84. Balmer, J.E.; Blomhoff, R. Gene expression regulation by retinoic acid. J. Lipid Res. 2002, 43, 1773-1808.
85. Kambhampati, S.; Li, Y.; Verma, A.; Sassano, A.; Majchrzak, B.; Deb, D.K.; Parmar, S.; Giafis, N.; Kalvakolanu, D.V.; Rahman, A. et al Activation of protein kinase C 6 by all- trans-retinoic acid. J. Biol. Chem. 2003, 278, 32544-32551.
86. Zheng, B.; Han, M.; Shu, Y.N.; Li, Y.J.; Miao, SB.; Zhang, X.H.; Shi, H.J.; Zhang, T.; Wen, J.K. HDAC2 phosphorylation-dependent Klf5 deacetylation and RARa acetylation induced by RAR agonist switch the transcription regulatory programs of p21 in VSMCs. Cell Res. 2011, 21, 1487-1508.
87. Petkovich, M.; Brand, N.J.; Krust, A.; Chambon, P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 1987, 330, 444-450.
88. Giguere, V.; Ong, E.S.; Segui, P.; Evans, R.M. Identification of a receptor for the morphogen retinoic acid. Nature 1987, 330, 624-629.
89. Evans, R. A transcriptional basis for physiology. Nat. Med. 2004, 10, 1022-1026.
90. Chambon, P. How I became one of the fathers of a superfamily. Nat. Med. 2004, 10, 1027-1031.
91. Leroy, P.; Krust, A.; Zelent, A.; Mendelsohn, C.; Garnier, J.M.; Kastner, P.; Dierich, A.; Chambon, P. Multiple isoforms of the mouse retinoic acid receptor a are generated by alternative splicing and differential induction by retinoic acid. EMBO J. 1991, 10, 59-69.
92. Brocard, J.; Kastner, P.; Chambon, P. Two novel RXR a isoforms from mouse testis. Biochem. Biophys. Res. Commun. 1996, 229, 211-218.
93. Peng, X.; Maruo, T.; Cao, Y.; Punj, V.; Mehta, R.; Das Gupta, T.K.; Christov, K. A novel RARp isoform directed by a distinct promoter P3 and mediated by retinoic acid in breast cancer cells. Cancer Res. 2004, 64, 8911-8918.
94. Zelent, A.; Mendelsohn, C.; Kastner, P.; Krust, A.; Garnier, J.M.; Ruffenach, F.; Leroy, P.; Chambon, P. Differentially expressed isoforms of the mouse retinoic acid receptor p generated by usage of two promoters and alternative splicing. EMBO J. 1991, 10, 71-81.
95. Kastner, P.; Krust, A.; Mendelsohn, C.; Garnier, J.M.; Zelent, A.; Leroy, P.; Staub, A.; Chambon, P. Murine isoforms of retinoic acid receptor y with specific patterns of expression. Proc. Natl. Acad. Sci. USA 1990, 87, 2700-2704.
96. Dolle, P.; Ruberte, E.; Kastner, P.; Petkovich, M.; Stoner, CM.; Gudas, L.J.; Chambon, P. Differential expression of genes encoding a, p and y retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 1989, 342, 702-705.
97. Dolle, P.; Ruberte, E.; Leroy, P.; Morriss-Kay, G.; Chambon, P. Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development 1990, 110, 1133-1151.
98. Ruberte, E.; Dolle, P.; Chambon, P.; Morriss-Kay, G. Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 1991, 111, 45-60.
99. Ruberte, E.; Friederich, V.; Chambon, P.; Morriss-Kay, G. Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development 1993, 118, 267-282.
100. Mark, M.; Ghyselinck, N.B.; Chambon, P. Function of retinoic acid receptors during embryonic development. Nucl. Recept. Signal. 2009, 7, e002.
101. Theodosiou, M.; Laudet, V.; Schubert, M. From carrot to clinic: An overview of the retinoic acid signaling pathway. Cell. Mol. Life Sci. 2010, 67, 1423-1445.
102. Krezel, W.; Ghyselinck, N.; Samad, T.A.; Dupe, V.; Kastner, P.; Borrelli, E.; Chambon, P. Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 1998, 279, 863-867.
103. Liao, W.L.; Tsai, H.C.; Wang, H.F.; Chang, J.; Lu, KM.; Wu, H.L.; Lee, Y.C.; Tsai, T.F.; Takahashi, H.; Wagner, M. et al. Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proc. Natl. Acad. Sci. USA 2008, 105, 6765-6770.
104. Lohnes, D.; Kastner, P.; Dierich, A.; Mark, M.; LeMeur, M.; Chambon, P. Function of retinoic acid receptor y in the mouse. Cell 1993, 73, 643-658.
105. Brun, P.J.; Grijalva, A.; Rausch, R.; Watson, E.; Yuen, J.J.; Das, B.C.; Shudo, K.; Kagechika, H.; Leibel, R.L.; Blaner, W.S. Retinoic acid receptor signaling is required to maintain glucose-stimulated insulin secretion and p-cell mass. FASEB J. 2015, 29, 671-683.
106. Berry, D.C.; Noy, N. All- trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor p/8 and retinoic acid receptor. Mol. Cell. Biol. 2009, 29, 3286-3296.
107. Berry, D.C.; DeSantis, D.; Soltanian, H.; Croniger, CM.; Noy, N. Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress diet-induced obesity. Diabetes 2012, 61, 1112-1121.
108. Scribner, K.B.; Odom, D.P.; McGrane, M.M. Nuclear receptor binding to the retinoic acid response elements of the phosphoenolpyruvate carboxykinase gene in vivo: Effects of vitamin A deficiency. J. Nutr. Biochem. 2007, 18, 206-214.
109. Zhang, Y.; Li, R.; Chen, W.; Li, Y.; Chen, G. Retinoids induced Pck1 expression and attenuated insulin-mediated suppression of its expression via activation of retinoic acid receptor in primary rat hepatocytes. Mol. Cell. Biochem. 2011, 355, 1-8.
110. Kane, M.A.; Chen, N.; Sparks, S.; Napoli, J.L. Quantification of endogenous retinoic acid in limited biological samples by LC/MS/MS. Biochem. J. 2005, 388, 363-369.
111. Kane, M.A.; Folias, A.E.; Pingitore, A.; Perri, M.; Obrochta, KM.; Krois, C.R.; Cione, E.; Ryu, J. Y; Napoli, J.L. Identification of 9-c-retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion. Proc. Natl. Acad. Sci. USA 2010, 107, 21884-21889.
112. De Urquiza, A.M.; Liu, S.; Sjoberg, M.; Zetterstrom, R.H.; Griffiths, W.; Sjovall, J.; Perlmann, T. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000, 290, 2140-2144.
113. Ziouzenkova, O.; Orasanu, G.; Sukhova, G; Lau, E.; Berger, J.P.; Tang, G; Krinsky, N.I.; Dolnikowski, G.G.; Plutzky, J. Asymmetric cleavage of P-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Mol. Endocrinol. 2007, 21, 77-88.
114. Lefebvre, P.; Benomar, Y.; Staels, B. Retinoid X receptors: Common heterodimerization partners with distinct functions. Trends Endocrinol. Metab. 2010, 21, 676-683.
115. Mangelsdorf, D.J.; Ong, E.S.; Dyck, J.A.; Evans, R.M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 1990, 345, 224-229.
116. Mangelsdorf, D.J.; Borgmeyer, U.; Heyman, R.A.; Zhou, J.Y.; Ong, E.S.; Oro, A.E.; Kakizuka, A.; Evans, R.M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992, 6, 329-344.
117. Dolle, P.; Fraulob, V.; Kastner, P.; Chambon, P. Developmental expression of murine retinoid X receptor (RXR) genes. Mech. Dev. 1994, 45, 91-104.
118. Mark, M.; Ghyselinck, N.B.; Chambon, P. Function of retinoid nuclear receptors: Lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu. Rev. Pharmacol. Toxicol. 2006, 46, 451-480.
119. Krezel, W.; Dupe, V.; Mark, M.; Dierich, A.; Kastner, P.; Chambon, P. RXR y null mice are apparently normal and compound RXRa^/RXRp^/RXRy^ mutant mice are viable. Proc. Natl. Acad. Sci. USA 1996, 93, 9010-9014.
120. Cooney, A.J.; Leng, X.; Tsai, S.Y.; O’Malley, B.W.; Tsai, M.J. Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors. J. Biol. Chem. 1993, 268, 4152-4160.
121. Blumberg, B.; Evans, R.M. Orphan nuclear receptors-New ligands and new possibilities. Genes Dev. 1998, 12, 3149-3155.
122. Mascrez, B.; Mark, M.; Krezel, W.; Dupe, V.; LeMeur, M.; Ghyselinck, N.B.; Chambon, P. Differential contributions of AF-1 and AF-2 activities to the developmental functions of RXR a. Development 2001, 128, 2049-2062.
123. Li, D.; Li, T.; Wang, F.; Tian, H.; Samuels, H.H. Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer. Mol. Cell. Biol. 2002, 22, 5782-5792.
124. Singh Ahuja, H.; Liu, S.; Crombie, D.L.; Boehm, M.; Leibowitz, M.D.; Heyman, R.A.; Depre, C; Nagy, L.; Tontonoz, P.; Davies, P.J. Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Mol. Pharmacol. 2001, 59, 765-773.
125. Li, R.; Chen, W.; Li, Y.; Zhang, Y.; Chen, G. Retinoids synergized with insulin to induce Srebp-1c expression and activated its promoter via the two liver X receptor binding sites that mediate insulin action. Biochem. Biophys. Res. Commun. 2011, 406, 268-272.
126. Mukherjee, R.; Davies, P.J.; Crombie, D.L.; Bischoff, E.D.; Cesario, R.M.; Jow, L.; Hamann, L.G.; Boehm, M.F.; Mondon, C.E.; Nadzan, A.M. et al. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 1997, 386, 407-410.
127. Wan, Y.J.; Han, G.; Cai, Y.; Dai, T.; Konishi, T.; Leng, A.S. Hepatocyte retinoid X receptor-a-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance. Endocrinology 2003, 144, 605-611.
128. Metzger, D.; Imai, T.; Jiang, M.; Takukawa, R.; Desvergne, B.; Wahli, W.; Chambon, P. Functional role of RXRs and PPARy in mature adipocytes. Prostaglandins Leukot. Essent. Fat. Acids 2005, 73, 51-58.
129. Ravnskjaer, K.; Boergesen, M.; Rubi, B.; Larsen, J.K.; Nielsen, T.; Fridriksson, J.; Maechler, P.; Mandrup, S. Peroxisome proliferator-activated receptor a (PPARa) potentiates, whereas PPARy attenuates, glucose-stimulated insulin secretion in pancreatic p cells. Endocrinology 2005, 146, 3266-3276.
130. Miyazaki, S.; Taniguchi, H.; Moritoh, Y.; Tashiro, F.; Yamamoto, T.; Yamato, E.; Ikegami, H.; Ozato, K.; Miyazaki, J. Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic p cells. Diabetes 2010, 59, 2854-2861.
131. Costa, R.H.; Grayson, D.R.; Darnell, J.E. Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and a 1-antitrypsin genes. Mol Cell. Biol. 1989, 9, 1415-1425.
132. Sladek, F.M.; Zhong, W.M.; Lai, E.; Darnell, J.E. Liver-enriched transcription factor HNF4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990, 4, 2353-2365.
133. Drewes, T.; Senkel, S.; Holewa, B.; Ryffel, G.U. Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol. Cell. Biol. 1996, 16, 925-931.
134. Ellard, S.; Colclough, K. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1a (HNF1A) and 4a (HNF4A) in maturity-onset diabetes of the young. Hum. Mutat. 2006, 27, 854-869.
135. Thomas, H.; Jaschkowitz, K.; Bulman, M.; Frayling, T.M.; Mitchell, S.M.; Roosen, S.; Lingott-Frieg, A.; Tack, C.J.; Ellard, S.; Ryffel, G.U. et al. A distant upstream promoter of the HNF4a gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum. Mol. Genet. 2001, 10, 2089-2097.
136. Xie, X.; Liao, H.; Dang, H.; Pang, W.; Guan, Y.; Wang, X.; Shyy, J.Y.; Zhu, Y.; Sladek, F.M. Down-regulation of hepatic HNF4a gene expression during hyperinsulinemia via SREBPs. Mol. Endocrinol. 2009, 23, 434-443.
137. Eeckhoute, J.; Moerman, E.; Bouckenooghe, T.; Lukoviak, B.; Pattou, F.; Formstecher, P.; Kerr-Conte, J.; Vandewalle, B.; Laine, B. Hepatocyte nuclear factor 4 a isoforms originated from the P1 promoter are expressed in human pancreatic p cells and exhibit stronger transcriptional potentials than P2 promoter-driven isoforms. Endocrinology 2003, 144, 1686-1694.
138. Stoffel, M.; Duncan, S.A. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4a regulates expression of genes required for glucose transport and metabolism. Proc. Natl. Acad. Sci. USA 1997, 94, 13209-13214.
139. Jiang, G.; Nepomuceno, L.; Hopkins, K.; Sladek, F.M. Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors. Mol. Cell. Biol. 1995, 15, 5131-5143.
140. Bolotin, E.; Liao, H.; Ta, T.C.; Yang, C.; Hwang-Verslues, W.; Evans, J.R.; Jiang, T.; Sladek, F.M. Integrated approach for the identification of human hepatocyte nuclear factor 4α target genes using protein binding microarrays. Hepatology 2010, 51, 642–653.
141. Jiang, G.; Nepomuceno, L.; Yang, Q.; Sladek, F.M. Serine/threonine phosphorylation of orphan receptor hepatocyte nuclear factor 4. Arch. Biochem. Biophys. 1997, 340, 1–9.
142. Viollet, B.; Kahn, A.; Raymondjean, M. Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4. Mol. Cell. Biol. 1997, 17, 4208–4219.
143. Duncan, S.A.; Manova, K.; Chen, W.S.; Hoodless, P.; Weinstein, D.C.; Bachvarova, R.F.; Darnell, J.E., Expression of transcription factor HNF4 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. USA 1994, 91, 7598–7602.
144. Taraviras, S.; Monaghan, A.P.; Schutz, G.; Kelsey, G. Characterization of the mouse HNF4 gene and its expression during mouse embryogenesis. Mech. Dev. 1994, 48, 67–79.
145. Chen, W.S.; Manova, K.; Weinstein, D.C.; Duncan, S.A.; Plump, A.S.; Prezioso, V.R.; Bachvarova, R.F.; Darnell, J.E. Disruption of the HNF4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev. 1994, 8, 2466–2477.
146. Duncan, S.A.; Nagy, A.; Chan, W. Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: Tetraploid rescue of HNF4-/- embryos. Development 1997, 124, 279–287.
147. Kiselyuk, A.; Lee, S.H.; Farber-Katz, S.; Zhang, M.; Athavankar, S.; Cohen, T.; Pinkerton, A.B.; Ye, M.; Bushway, P.; Richardson, A.D.; et al. HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem. Biol. 2012, 19, 806–818.
148. Hayhurst, G.P.; Lee, Y.H.; Lambert, G.; Ward, J.M.; Gonzalez, F.J. Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol. Cell. Biol. 2001, 21, 1393–1403.
149. Palanker, L.; Tennessen, J.M.; Lam, G.; Thummel, C.S. Drosophila HNF4 regulates lipid mobilization and β-oxidation. Cell Metab. 2009, 9, 228–239.
150. Ganjam, G.K.; Dimova, E.Y.; Unterman, T.G.; Kietzmann, T. FoxO1 and HNF4 are involved in regulation of hepatic glucokinase gene expression by resveratrol. J. Biol. Chem. 2009, 284, 30783–30797.
151. Roth, U.; Jungermann, K.; Kietzmann, T. Activation of glucokinase gene expression by hepatic nuclear factor 4α in primary hepatocytes. Biochem. J. 2002, 365, 223–228.
152. Hirota, K.; Sakamaki, J.; Ishida, J.; Shimamoto, Y.; Nishihara, S.; Kodama, N.; Ohta, K.; Yamamoto, M.; Tanimoto, K.; Fukamizu, A. A combination of HNF4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding. J. Biol. Chem. 2008, 283, 32432–32441.
153. Miura, A.; Yamagata, K.; Kakei, M.; Hatakeyama, H.; Takahashi, N.; Fukui, K.; Nammo, T.; Yoneda, K.; Inoue, Y.; Sladek, F.M. et al. Hepatocyte nuclear factor 4α is essential for glucose-stimulated insulin secretion by pancreatic β cells. J. Biol. Chem. 2006, 281, 5246–5257.
154. Bartoov-Shifman, R.; Hertz, R.; Wang, H.; Wollheim, C.B.; Bar-Tana, J.; Walker, M.D. Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4α. J. Biol. Chem. 2002, 277, 25914–25919.
155. Wang, H.; Maechler, P.; Antinozzi, P.A.; Hagenfeldt, K.A.; Wollheim, C.B. Hepatocyte nuclear factor 4α regulates the expression of pancreatic β cell genes implicated in glucose metabolism and nutrient-induced insulin secretion. J. Biol. Chem. 2000, 275, 35953–35959.
156. Yamagata, K.; Furuta, H.; Oda, N.; Kaisaki, P.J.; Menzel, S.; Cox, N.J.; Fajans, S.S.; Signorini, S.; Stoffel, M.; Bell, G.I. Mutations in the hepatocyte nuclear factor 4α gene in maturity-onset diabetes of the young (MODY1). Nature 1996, 384, 458–460.
157. Moller, A.M.; Dalgaard, L.T.; Ambye, L.; Hansen, L.; Schmitz, O.; Hansen, T.; Pedersen, O. A novel Phe75fsdelT mutation in the hepatocyte nuclear factor 4α gene in a Danish pedigree with maturity-onset diabetes of the young. J. Clin. Endocrinol. Metab. 1999, 84, 367–369.
158. Lehto, M.; Bitzen, P.O.; Isomaa, B.; Wipemo, C.; Wessman, Y.; Forsblom, C.; Tuomi, T.; Taskinen, M.R.; Groop, L. Mutation in the HNF4α gene affects insulin secretion and triglyceride metabolism. Diabetes 1999, 48, 423–425.
159. Lindner, T.; Gragnoli, C.; Furuta, H.; Cockburn, B.N.; Petzold, C.; Rietzsch, H.; Weiss, U.; Schulze, J.; Bell, G.I. Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor 4α/MODY1 gene. J. Clin. Investig. 1997, 100, 1400–1405.
160. Malecki, M.T.; Yang, Y.; Antonellis, A.; Curtis, S.; Warram, J.H.; Krolewski, A.S. Identification of new mutations in the hepatocyte nuclear factor 4α gene among families with early onset type 2 diabetes mellitus. Diabet. Med. 1999, 16, 193–200.
161. Furuta, H.; Iwasaki, N.; Oda, N.; Hinokio, Y.; Horikawa, Y.; Yamagata, K.; Yano, N.; Sugahiro, J.; Ogata, M.; Ohgawara, H. et al. 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 1997, 46, 1652–1657.
162. Moller, A.M.; Urhammer, S.A.; Dalgaard, L.T.; Reneland, R.; Berglund, L.; Hansen, T.; Clausen, J.O.; Lithell, H.; Pedersen, O. Studies of the genetic variability of the coding region of the hepatocyte nuclear factor 4α in Caucasians with maturity onset NIDDM. Diabetologia 1997, 40, 980–983.
163. Bulman, M.P.; Dronsfield, M.J.; Frayling, T.; Appleton, M.; Bain, S.C.; Ellard, S.; Hattersley, A.T. A missense mutation in the hepatocyte nuclear factor 4α gene in a UK pedigree with maturity-onset diabetes of the young. Diabetologia 1997, 40, 859–862.
164. Hani, E.H.; Suaud, L.; Boutin, P.; Chevre, J.C.; Durand, E.; Philippi, A.; Demenais, F.; Vionnet, N.; Furuta, H.; Velho, G. et al. A missense mutation in hepatocyte nuclear factor 4α, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. J. Clin. Investig. 1998, 101, 521–526.
165. Love-Gregory, L.D.; Wasson, J.; Ma, J.; Jin, C.H.; Glaser, B.; Suarez, B.K.; Permutt, M.A. A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor 4α gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an Ashkenazi Jewish population. Diabetes 2004, 53, 1134–1140.
166. Silander, K.; Mohlke, K.L.; Scott, L.J.; Peck, E.C.; Hollstein, P.; Skol, A.D.; Jackson, A.U.; Deloukas, P.; Hunt, S.; Stavrides, G. et al. Genetic variation near the hepatocyte nuclear factor 4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 2004, 53, 1141–1149.
167. Weedon, M.N.; Owen, K.R.; Shields, B.; Hitman, G.; Walker, M.; McCarthy, M.I.; Love-Gregory, L.D.; Permutt, M.A.; Hattersley, A.T.; Frayling, T.M. Common variants of the hepatocyte nuclear factor-4α P2 promoter are associated with type 2 diabetes in the UK. population. Diabetes 2004, 53, 3002–3006.
168. Hertz, R.; Magenheim, J.; Berman, I.; Bar-Tana, J. Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor 4α. Nature 1998, 392, 512–516.
169. Wisely, G.B.; Miller, A.B.; Davis, R.G.; Thornquest, A.D.; Johnson, R.; Spitzer, T.; Sefler, A.; Shearer, B.; Moore, J.T.; Miller, A.B. et al. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure 2002, 10, 1225–1234.
170. Dhe-Paganon, S.; Duda, K.; Iwamoto, M.; Chi, Y.I.; Shoelson, S.E. Crystal structure of the HNF4α ligand binding domain in complex with endogenous fatty acid ligand. J. Biol. Chem. 2002, 277, 37973–37976.
171. Divine, J.K.; McCaul, S.P.; Simon, T.C. HNF-1α and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 285, G62–G72.
172. Hatzis, P.; Talianidis, I. Regulatory mechanisms controlling human hepatocyte nuclear factor 4α gene expression. Mol. Cell. Biol. 2001, 21, 7320–7330.
173. Eeckhoute, J.; Formstecher, P.; Laine, B. Hepatocyte nuclear factor 4α enhances the hepatocyte nuclear factor 1α-mediated activation of transcription. Nucleic Acids Res. 2004, 32, 2586–2593.
174. Ktistaki, E.; Talianidis, I. Modulation of hepatic gene expression by hepatocyte nuclear factor 1. Science 1997, 277, 109–112.
175. Rowley, C.W.; Staloch, L.J.; Divine, J.K.; McCaul, S.P.; Simon, T.C. Mechanisms of mutual functional interactions between HNF4α and HNF1α revealed by mutations that cause maturity onset diabetes of the young. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G466–G475.
176. Suaud, L.; Hemimou, Y.; Formstecher, P.; 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 1999, 48, 1162–1167.
177. Hall, R.K.; Sladek, F.M.; Granner, D.K.The orphan receptors COUP-TF and HNF4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. Proc. Natl. Acad. Sci. USA 1995, 92, 412–416.
178. Stroup, D.; Chiang, J.Y. HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7α-hydroxylase gene (CYP7A1). J. Lipid Res. 2000, 41, 1–11.
179. Chan, J.; Nakabayashi, H.; Wong, N.C. HNF4 increases activity of the rat Apo A1 gene. Nucleic Acids Res. 1993, 21, 1205–1211.
180. Ladias, J.A.; Hadzopoulou-Cladaras, M.; Kardassis, D.; Cardot, P.; Cheng, J.; Zannis, V.; Cladaras, C. Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF4, ARP-1, EAR-2, and EAR-3. J. Biol. Chem. 1992, 267, 15849–15860.
181. Mietus-Snyder, M.; Sladek, F.M.; Ginsburg, G.S.; Kuo, C.F.; Ladias, J.A.; Darnell, J.E.; Karathanasis, S.K. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol. Cell. Biol. 1992, 12, 1708–1718.
182. Ktistaki, E.; Talianidis, I. Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression. Mol. Cell. Biol. 1997, 17, 2790–2797.
183. Magee, T.R.; Cai, Y.; El-Houseini, M.E.; Locker, J.; Wan, Y.J. Retinoic acid mediates down-regulation of the α-fetoprotein gene through decreased expression of hepatocyte nuclear factors. J. Biol. Chem. 1998, 273, 30024–30032.
184. Nakshatri, H.; Chambon, P. The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF4, and ARP-1 homo- and heterodimers. J. Biol. Chem. 1994, 269, 890–902.
185. Makita, T.; Hernandez-Hoyos, G.; Chen, T.H.; Wu, H.; Rothenberg, E.V.; Sucov, H.M. A developmental transition in definitive erythropoiesis: Erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4. Genes Dev. 2001, 15, 889–901.
186. Pastorcic, M.; Wang, H.; Elbrecht, A.; Tsai, S.Y.; Tsai, M.J.; O’Malley, B.W. Control of transcription initiation in vitro requires binding of a transcription factor to the distal promoter of the ovalbumin gene. Mol. Cell. Biol. 1986, 6, 2784–2791.
187. Sagami, I.; Tsai, S.Y.; Wang, H.; Tsai, M.J.; O’Malley, B.W. Identification of two factors required for transcription of the ovalbumin gene. Mol. Cell. Biol. 1986, 6, 4259–4267.
188. Achatz, G.; Holzl, B.; Speckmayer, R.; Hauser, C.; Sandhofer, F.; Paulweber, B. Functional domains of the human orphan receptor ARP-1/COUP-TFII involved in active repression and transrepression. Mol. Cell. Biol. 1997, 17, 4914–4932.
189. Leng, X.; Cooney, A.J.; Tsai, S.Y.; Tsai, M.J. Molecular mechanisms of COUP-TF-mediated transcriptional repression: Evidence for transrepression and active repression. Mol. Cell. Biol. 1996, 16, 2332–2340.
190. Zhang, P.; Bennoun, M.; Gogard, C.; Bossard, P.; Leclerc, I.; Kahn, A.; Vasseur-Cognet, M. Expression of COUP-TFII in metabolic tissues during development. Mech. Dev. 2002, 119, 109–114.
191. Wang, L.H.; Ing, N.H.; Tsai, S.Y.; O’Malley, B.W.; Tsai, M.J. The COUP-TFs compose a family of functionally related transcription factors. Gene Expr. 1991, 1, 207–216.
192. Ladias, J.A.; Karathanasis, S.K. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science 1991, 251, 561–565.
193. Qiu, Y.; Krishnan, V.; Pereira, F.A.; Tsai, S.Y.; Tsai, M.J. Chicken ovalbumin upstream promoter-transcription factors and their regulation. J. Steroid Biochem. Mol. Biol. 1996, 56, 81–85.
194. Pereira, F.A.; Qiu, Y.; Zhou, G.; Tsai, M.J.; Tsai, S.Y. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev. 1999, 13, 1037–1049.
195. Takamoto, N.; Kurihara, I.; Lee, K.; Demayo, F.J.; Tsai, M.J.; Tsai, S.Y. Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. Mol. Endocrinol. 2005, 19, 2299–2308.
196. Da Silva, S.L.; van Horssen, A.M.; Chang, C.; Burbach, J.P. Expression of nuclear hormone receptors in the rat supraoptic nucleus. Endocrinology 1995, 136, 2276–2283.
197. Sabra-Makke, L.; Tourrel-Cuzin, C.; Denis, R.G.; Moldes, M.; Pegorier, J.P.; Luquet, S.; Vasseur-Cognet, M.; Bossard, P. The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway. PLoS ONE 2010, 5, e13464.
198. Bardoux, P.; Zhang, P.; Flamez, D.; Perilhou, A.; Lavin, T.A.; Tanti, J.F.; Hellemans, K.; Gomas, E.; Godard, C.; Andreelli, F. et al. Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout. Diabetes 2005, 54, 1357–1363.
199. Gupta, R.K.; Vatamaniuk, M.Z.; Lee, C.S.; Flaschen, R.C.; Fulmer, J.T.; Matschinsky, F.M.; Duncan, S.A.; Kaestner, K.H. The MODY1 gene HNF4α regulates selected genes involved in insulin secretion. J. Clin. Investig. 2005, 115, 1006–1015.
200. Pearson, E.R.; Boj, S.F.; Steele, A.M.; Barrett, T.; Stals, K.; Shield, J.P.; Ellard, S.; Ferrer, J.; Hattersley, A.T. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4α gene. PLoS Med. 2007, 4, e118.
201. Perilhou, A.; Tourrel-Cuzin, C.; Kharroubi, I.; Henique, C.; Fauveau, V.; Kitamura, T.; Magnan, C.; Postic, C.; Prip-Buus, C.; Vasseur-Cognet, M. The transcription factor COUP-TFII is negatively regulated by insulin and glucose via Foxo1- and ChREBP-controlled pathways. Mol. Cell. Biol. 2008, 28, 6568–6579.
202. Li, L.; Xie, X.; Qin, J.; Jeha, G.S.; Saha, P.K.; Yan, J.; Haueter, C.M.; Chan, L.; Tsai, S.Y.; Tsai, M.J. The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metab. 2009, 9, 77–87.
203. Xu, Z.; Yu, S.; Hsu, C.H.; Eguchi, J.; Rosen, E.D. The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis. Proc. Natl. Acad. Sci. USA 2008, 105, 2421–2426.
204. Myers, S.A.; Wang, S.C.; Muscat, G.E. The chicken ovalbumin upstream promoter-transcription factors modulate genes and pathways involved in skeletal muscle cell metabolism. J. Biol. Chem. 2006, 281, 24149–24160.
205. Crowther, L.M.; Wang, S.C.; Eriksson, N.A.; Myers, S.A.; Murray, L.A.; Muscat, G.E. Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells. Physiol. Genomics 2011, 43, 213–227.
206. Okamura, M.; Kudo, H.; Wakabayashi, K.; Tanaka, T.; Nonaka, A.; Uchida, A.; Tsutsumi, S.; Sakakibara, I.; Naito, M.; Osborne, T.F. et al. COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis. Proc. Natl. Acad. Sci. USA 2009, 106, 5819–5824.
207. Benoit, G.; Cooney, A.; Giguere, V.; Ingraham, H.; Lazar, M.; Muscat, G.; Perlmann, T.; Renaud, J.P.; Schwabe, J.; Sladek, F. et al. International union of pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 2006, 58, 798–836.
208. Perilhou, A.; Tourrel-Cuzin, C.; Zhang, P.; Kharroubi, I.; Wang, H.; Fauveau, V.; Scott, D.K.; Wollheim, C.B.; Vasseur-Cognet, M. The MODY1 gene for hepatocyte nuclear factor 4α and a feedback loop control COUP-TFII expression in pancreatic β cells. Mol. Cell. Biol. 2008, 28, 4588–4597.
209. Park, J.I.; Tsai, S.Y.; Tsai, M.J. Molecular mechanism of chicken ovalbumin upstream promoter-transcription factor (COUP-TF) actions. Keio J. Med. 2003, 52, 174–181.
210. Malik, S.; Karathanasis, S. Transcriptional activation by the orphan nuclear receptor ARP-1. Nucleic Acids Res. 1995, 23, 1536–1543.
211. Qiu, Y.; Tsai, S.Y.; Tsai, M.J. COUP-TF an orphan member of the steroid/thyroid hormone receptor superfamily. Trends Endocrinol. Metab. 1994, 5, 234–239.
212. Marcus, S.L.; Winrow, C.J.; Capone, J.P.; Rachubinski, R.A. A p56lck ligand serves as a coactivator of an orphan nuclear hormone receptor. J. Biol. Chem. 1996, 271, 27197–27200.
213. Jonk, L.J.; de Jonge, M.E.; Pals, C.E.; Wissink, S.; Vervaart, J.M.; Schoorlemmer, J.; Kruijer, W. Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Mech. Dev. 1994, 47, 81–97.
214. Tsai, S.Y.; Tsai, M.J. Chick ovalbumin upstream promoter-transcription factors (COUP-TFs): Coming of age. Endocr. Rev. 1997, 18, 229–240.
215. Litchfield, L.M.; Riggs, K.A.; Hockenberry, A.M.; Oliver, L.D.; Barnhart, K.G.; Cai, J.; Pierce, W.M., Jr.; Ivanova, M.M.; Bates, P.J.; Appana, S.N. et al. Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells. PLoS ONE 2012, 7, e38278.
216. Doi, T.; Sugimoto, K.; Puri, P. Prenatal retinoic acid up-regulates pulmonary gene expression of COUP-TFII, FOG2, and GATA4 in pulmonary hypoplasia. J. Pediatr. Surg. 2009, 44, 1933–1937.
217. Fjose, A.; Weber, U.; Mlodzik, M. A novel vertebrate svp-related nuclear receptor is expressed as a step gradient in developing rhombomeres and is affected by retinoic acid. Mech. Dev. 1995, 52, 233–246.
218. Malpel, S.; Mendelsohn, C.; Cardoso, W.V. Regulation of retinoic acid signaling during lung morphogenesis. Development 2000, 127, 3057–3067.
219. Prahalad, P.; Dakshanamurthy, S.; Ressom, H.; Byers, S.W. Retinoic acid mediates regulation of network formation by COUP-TFII and VE-cadherin expression by TGFβ receptor kinase in breast cancer cells. PLoS ONE 2010, 5, e10023.
220. Neels, J.G.; Grimaldi, P.A. Physiological functions of peroxisome proliferator-activated receptor beta. Physiol. Rev. 2014, 94, 795–858.
221. Sher, T.; Yi, H.F.; McBride, O.W.; Gonzalez, F.J. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993, 32, 5598–5604.
222. Yoshikawa, T.; Brkanac, Z.; Dupont, B.R.; Xing, G.Q.; Leach, R.J.; Detera-Wadleigh, S.D. Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2. Genomics 1996, 35, 637–638.
223. Greene, M.E.; Blumberg, B.; McBride, O.W.; Yi, H.F.; Kronquist, K.; Kwan, K.; Hsieh, L.; Greene, G.; Nimer, S.D. Isolation of the human peroxisome proliferator activated receptor γ cDNA: Expression in hematopoietic cells and chromosomal mapping. Gene Expr. 1995, 4, 281–299.
224. Berger, J.; Moller, D.E. The mechanisms of action of PPARs. Annu. Rev. Med. 2002, 53, 409–435.
225. Issemann, I.; Prince, R.A.; Tugwood, J.D.; Green, S. The peroxisome proliferator-activated receptor: Retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs. J. Mol. Endocrinol. 1993, 11, 37–47.
226. Zhu, Y.; Qi, C.; Korenberg, J.R.; Chen, X.N.; Noya, D.; Rao, M.S.; Reddy, J.K. Structural organization of mouse peroxisome proliferator-activated receptor γ (mPPAR γ) gene: Alternative promoter use and different splicing yield two mPPAR γ isoforms. Proc. Natl. Acad. Sci. USA 1995, 92, 7921–7925.
227. Tontonoz, P.; Hu, E.; Graves, R.A.; Budavari, A.I.; Spiegelman, B.M. mPPARy 2: Tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994, 8, 1224-1234.
228. Escher, P.; Braissant, O.; Basu-Modak, S.; Michalik, L.; Wahli, W.; Desvergne, B. Rat PPARs: Quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 2001, 142, 4195-4202.
229. Holst, D.; Luquet, S.; Nogueira, V.; Kristiansen, K.; Leverve, X.; Grimaldi, P.A. Nutritional regulation and role of peroxisome proliferator-activated receptor 6 in fatty acid catabolism in skeletal muscle. Biochim. Biophys. Acta 2003, 1633, 43-50.
230. Wang, Y.X.; Lee, C.H.; Tiep, S.; Yu, R.T.; Ham, J.; Kang, H.; Evans, R.M. Peroxisome-proliferator-activated receptor 6 activates fat metabolism to prevent obesity. Cell 2003, 113, 159-170.
231. Luquet, S.; Lopez-Soriano, J.; Holst, D.; Fredenrich, A.; Melki, J.; Rassoulzadegan, M.; Grimaldi, P.A. Peroxisome proliferator-activated receptor 6 controls muscle development and oxidative capability. FASEB J. 2003, 17, 2299-2301.
232. Wang, Y.X.; Zhang, C.L.; Yu, R.T.; Cho, H.K.; Nelson, M.C.; Bayuga-Ocampo, C.R.; Ham, J.; Kang, H.; Evans, R.M. Regulation of muscle fiber type and running endurance by PPAR6. PLoS Biol. 2004, 2, e294.
233. Tanaka, T; Yamamoto, J.; Iwasaki, S.; Asaba, H; Hamura, H; Ikeda, Y; Watanabe, M.; Magoori, K.; Ioka, R.X.; Tachibana, K. et al. Activation of peroxisome proliferator-activated receptor 6 induces fatty acid P-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc. Natl. Acad. Sci. USA 2003, 100, 15924-15929.
234. IJpenberg, A.; Jeannin, E.; Wahli, W.; Desvergne, B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J. Biol. Chem. 1997, 272, 20108-20117.
235. Palmer, C.N.; Hsu, M.H.; Griffin, H.J.; Johnson, E.F. Novel sequence determinants in peroxisome proliferator signaling. J. Biol. Chem. 1995, 270, 16114-16121.
236. Kliewer, S.A.; Umesono, K.; Noonan, D.J.; Heyman, R.A.; Evans, R.M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 1992, 358, 771–774.
237. Takata, Y.; Liu, J.; Yin, F.; Collins, A.R.; Lyon, C.J.; Lee, C.H.; Atkins, A.R.; Downes, M.; Barish, G.D.; Evans, R.M. et al. PPAR6-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc. Natl. Acad. Sci. USA 2008, 105, 4277-4282.
238. Yu, R.Y.; Wang, X.; Pixley, F.J.; Yu, J.J.; Dent, A.L.; Broxmeyer, HE.; Stanley, E.R.; Ye, B.H. BCL-6 negatively regulates macrophage proliferation by suppressing autocrine IL-6 production. Blood 2005, 105, 1777-1784.
239. Ali, FY.; Hall, M.G.; Desvergne, B.; Warner, T.D.; Mitchell, J.A. PPARp/6 agonists modulate platelet function via a mechanism involving PPAR receptors and specific association/repression of PKCa—Brief report. Arterioscler. Thromb. Vasc. Biol. 2009, 29, 1871-1873.
240. Rochette-Egly, C. Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA. Biochim. Biophys. Acta 2015, 1851, 66-75.
241. Shaw, N.; Elholm, M.; Noy, N. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor p/6. J. Biol. Chem. 2003, 278, 41589-41592.
242. Thulasiraman, P.; McAndrews, D.J.; Mohiudddin, I.Q. Curcumin restores sensitivity to retinoic acid in triple negative breast cancer cells. BMC Cancer 2014, 14, 724.
243. Budhu, A.; Gillilan, R.; Noy, N. Localization of the RAR interaction domain of cellular retinoic acid binding protein-II. J. Mol. Biol 2001, 305, 939-949.
244. Budhu, A.S.; Noy, N. Direct channeling of retinoic acid between cellular retinoic acid-binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest. Mol. Cell Biol 2002, 22, 2632-2641.
245. Yu, S.; Levi, L.; Siegel, R.; Noy, N. Retinoic acid induces neurogenesis by activating both retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor p/6 (PPARp/6). J. Biol Chem. 2012, 287, 42195-42205.
246. Garcia, A.D.; Ostapchuk, P.; Hearing, P. Functional interaction of nuclear factors EF-C, HNF4, and RXRa with hepatitis B virus enhancer I. J. Virol 1993, 67, 3940-3950.
247. Power, S.C.; Cereghini, S. Positive regulation of the vHNF1 promoter by the orphan receptors COUP-TF1/Ear3 and COUP-TFII/Arp1. Mol Cell Biol 1996, 16, 778-791.
248. Hertz, R.; Bishara-Shieban, J.; Bar-Tana, J. Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. J. Biol Chem. 1995, 270, 13470-13475.
249. Hertz, R.; Seckbach, M.; Zakin, M.M.; Bar-Tana, J. Transcriptional suppression of the transferrin gene by hypolipidemic peroxisome proliferators. J. Biol Chem. 1996, 271, 218-224.
250. Pineda Torra, I.; Jamshidi, Y.; Flavell, DM.; Fruchart, J.C.; Staels, B. Characterization of the human PPARa promoter: Identification of a functional nuclear receptor response element. Mol. Endocrinol 2002, 16, 1013-1028.
251. Mogilenko, D.A.; Dizhe, E.B.; Shavva, V.S.; Lapikov, I.A.; Orlov, S.V.; Perevozchikov, A.P. Role of the nuclear receptors HNF4 a, PPAR a, and LXRs in the TNF a-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells. Biochemistry 2009, 48, 11950-11960.
252. Yoon, J.C; Puigserver, P.; Chen, G; Donovan, J.; Wu, Z.; Rhee, J.; Adelmant, G.; Stafford, J.; Kahn, C.R.; Granner, D.K.; et al Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 2001, 413, 131-138.
253. Zhang, Y.; Li, R.; Li, Y.; Chen, W.; Zhao, S.; Chen, G. Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats. Biochem. Cell Biol 2012, 90, 548-557.
254. Noguchi, T.; Takenaka, M.; Yamada, K.; Matsuda, T.; Hashimoto, M.; Tanaka, T. Characterization of the 5' flanking region of rat glucokinase gene. Biochem. Biophys. Res. Commun. 1989, 164, 1247-1252.
255. Chen, G; Zhang, Y.; Lu, D.; Li, N.Q.; Ross, A.C. Retinoids synergize with insulin to induce hepatic Gck expression. Biochem. J. 2009, 419, 645-653.