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. 1996 Jul;16(7):3350–3360. doi: 10.1128/mcb.16.7.3350

Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor.

N Vu-Dac 1, K Schoonjans 1, V Kosykh 1, J Dallongeville 1, R A Heyman 1, B Staels 1, J Auwerx 1
PMCID: PMC231329  PMID: 8668150

Abstract

Considering the link between plasma high-density lipoprotein (HDL) cholesterol levels and a protective effect against coronary artery disease as well as the suggested beneficial effects of retinoids on the production of the major HDL apolipoprotein (apo), apo A-I, the goal of this study was to analyze the influence of retinoids on the expression of apo A-II, the other major HDL protein. Retinoic acid (RA) derivatives have a direct effect on hepatic apo A-II production, since all-trans (at) RA induces apo A-II mRNA levels and apo A-II secretion in primary cultures of human hepatocytes. In the HepG2 human hepatoblastoma cell line, both at-RA and 9-cis RA as well as the retinoid X receptor (RXR)-specific agonist LGD 1069, but not the RA receptor (RAR) agonist ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-pro penyl]-benzoic acid (TTNPB), induce apo A-II mRNA levels. Transient-transfection experiments with a reporter construct driven by the human apo A-II gene promoter indicated that 9-cis RA and at-RA, as well as the RXR agonists LGD 1069 and LG 100268, induced apo A-II gene expression at the transcriptional level. Only minimal effects of the RAR agonist TTNPB were observed on the apo A-II promoter reporter construct. Unilateral deletions and site-directed mutagenesis identified the J site of the apo A-II promoter mediating the responsiveness to RA. This element contains two imperfect half-sites spaced by 1 oligonucleotide. Cotransfection assays in combination with the use of RXR or RAR agonists showed that RXR but not RAR transactivates the apo A-II promoter through this element. By contrast, RAR inhibits the inductive effects of RXR on the apo A-II J site in a dose-dependent fashion. Gel retardation assays demonstrated that RXR homodimers bind, although with a lower affinity than RAR-RXR heterodimers, to the AH-RXR response element. In conclusion, retinoids induce hepatic apo A-II production at the transcriptional level via the interaction of RXR with an element in the J site containing two imperfect half-sites spaced by 1 oligonucleotide, thereby demonstrating an important role of RXR in controlling human lipoprotein metabolism. Since the J site also confers responsiveness of the apo A-II gene to fibrates and fatty acids via the activation of peroxisome proliferator-activated receptor-RXR heterodimers, this site can be considered a plurimetabolic response element.

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Selected References

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  1. Apfel R., Benbrook D., Lernhardt E., Ortiz M. A., Salbert G., Pfahl M. A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol. 1994 Oct;14(10):7025–7035. doi: 10.1128/mcb.14.10.7025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbaras R., Puchois P., Fruchart J. C., Ailhaud G. Cholesterol efflux from cultured adipose cells is mediated by LpAI particles but not by LpAI:AII particles. Biochem Biophys Res Commun. 1987 Jan 15;142(1):63–69. doi: 10.1016/0006-291x(87)90451-7. [DOI] [PubMed] [Google Scholar]
  3. Berthou L., Staels B., Saldicco I., Berthelot K., Casey J., Fruchart J. C., Denèfle P., Branellec D. Opposite in vitro and in vivo regulation of hepatic apolipoprotein A-I gene expression by retinoic acid. Absence of effects on apolipoprotein A-II gene expression. Arterioscler Thromb. 1994 Oct;14(10):1657–1664. doi: 10.1161/01.atv.14.10.1657. [DOI] [PubMed] [Google Scholar]
  4. Boehm M. F., Zhang L., Badea B. A., White S. K., Mais D. E., Berger E., Suto C. M., Goldman M. E., Heyman R. A. Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem. 1994 Sep 2;37(18):2930–2941. doi: 10.1021/jm00044a014. [DOI] [PubMed] [Google Scholar]
  5. Boehm M. F., Zhang L., Zhi L., McClurg M. R., Berger E., Wagoner M., Mais D. E., Suto C. M., Davies J. A., Heyman R. A. Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells. J Med Chem. 1995 Aug 4;38(16):3146–3155. doi: 10.1021/jm00016a018. [DOI] [PubMed] [Google Scholar]
  6. Bossu J. P., Chartier F. L., Vu-Dac N., Fruchart J. C., Laine B. Transcription of the human apolipoprotein A-II is down-regulated by the first intron of its gene. Biochem Biophys Res Commun. 1994 Jul 29;202(2):822–829. doi: 10.1006/bbrc.1994.2004. [DOI] [PubMed] [Google Scholar]
  7. Brewer H. B., Jr, Lux S. E., Ronan R., John K. M. Amino acid sequence of human apoLp-Gln-II (apoA-II), an apolipoprotein isolated from the high-density lipoprotein complex. Proc Natl Acad Sci U S A. 1972 May;69(5):1304–1308. doi: 10.1073/pnas.69.5.1304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cardot P., Chambaz J., Cladaras C., Zannis V. I. Regulation of the human ApoA-II gene by the synergistic action of factors binding to the proximal and distal regulatory elements. J Biol Chem. 1991 Dec 25;266(36):24460–24470. [PubMed] [Google Scholar]
  9. Cardot P., Chambaz J., Kardassis D., Cladaras C., Zannis V. I. Factors participating in the liver-specific expression of the human apolipoprotein A-II gene and their significance for transcription. Biochemistry. 1993 Sep 7;32(35):9080–9093. doi: 10.1021/bi00086a013. [DOI] [PubMed] [Google Scholar]
  10. Cardot P., Pastier D., Lacorte J. M., Mangeney M., Zannis V. I., Chambaz J. Purification and characterization of nuclear factors binding to the negative regulatory element D of human apolipoprotein A-II promoter: a negative regulatory effect is reversed by GABP, an Ets-related protein. Biochemistry. 1994 Oct 11;33(40):12139–12148. doi: 10.1021/bi00206a017. [DOI] [PubMed] [Google Scholar]
  11. Courey A. J., Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. doi: 10.1016/0092-8674(88)90144-4. [DOI] [PubMed] [Google Scholar]
  12. Davis K. D., Berrodin T. J., Stelmach J. E., Winkler J. D., Lazar M. A. Endogenous retinoid X receptors can function as hormone receptors in pituitary cells. Mol Cell Biol. 1994 Nov;14(11):7105–7110. doi: 10.1128/mcb.14.11.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Doolittle M. H., LeBoeuf R. C., Warden C. H., Bee L. M., Lusis A. J. A polymorphism affecting apolipoprotein A-II translational efficiency determines high density lipoprotein size and composition. J Biol Chem. 1990 Sep 25;265(27):16380–16388. [PubMed] [Google Scholar]
  14. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fidge N. H., Nestel P. J. Identification of apolipoproteins involved in the interaction of human high density lipoprotein3 with receptors on cultured cells. J Biol Chem. 1985 Mar 25;260(6):3570–3575. [PubMed] [Google Scholar]
  16. Fielding C. J., Fielding P. E. Molecular physiology of reverse cholesterol transport. J Lipid Res. 1995 Feb;36(2):211–228. [PubMed] [Google Scholar]
  17. Forman B. M., Umesono K., Chen J., Evans R. M. Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell. 1995 May 19;81(4):541–550. doi: 10.1016/0092-8674(95)90075-6. [DOI] [PubMed] [Google Scholar]
  18. Fried M. G., Crothers D. M. CAP and RNA polymerase interactions with the lac promoter: binding stoichiometry and long range effects. Nucleic Acids Res. 1983 Jan 11;11(1):141–158. doi: 10.1093/nar/11.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Giguère V. Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling. Endocr Rev. 1994 Feb;15(1):61–79. doi: 10.1210/edrv-15-1-61. [DOI] [PubMed] [Google Scholar]
  20. Hedrick C. C., Castellani L. W., Warden C. H., Puppione D. L., Lusis A. J. Influence of mouse apolipoprotein A-II on plasma lipoproteins in transgenic mice. J Biol Chem. 1993 Sep 25;268(27):20676–20682. [PubMed] [Google Scholar]
  21. Heery D. M., Pierrat B., Gronemeyer H., Chambon P., Losson R. Homo- and heterodimers of the retinoid X receptor (RXR) activated transcription in yeast. Nucleic Acids Res. 1994 Mar 11;22(5):726–731. doi: 10.1093/nar/22.5.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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 Jan 24;68(2):397–406. doi: 10.1016/0092-8674(92)90479-v. [DOI] [PubMed] [Google Scholar]
  23. Hussain M. M., Zannis V. I. Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins. Biochemistry. 1990 Jan 9;29(1):209–217. doi: 10.1021/bi00453a029. [DOI] [PubMed] [Google Scholar]
  24. Kaptein A., de Wit E. C., Princen H. M. Retinoids stimulate ApoA-I synthesis by induction of gene transcription in primary hepatocyte cultures from cynomolgus monkey (Macaca fascicularis) Arterioscler Thromb. 1993 Oct;13(10):1505–1514. doi: 10.1161/01.atv.13.10.1505. [DOI] [PubMed] [Google Scholar]
  25. Kliewer S. A., Umesono K., Mangelsdorf D. J., Evans R. M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. doi: 10.1038/355446a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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 Aug 27;358(6389):771–774. doi: 10.1038/358771a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Knott T. J., Eddy R. L., Robertson M. E., Priestley L. M., Scott J., Shows T. B. Chromosomal localization of the human apoprotein CI gene and of a polymorphic apoprotein AII gene. Biochem Biophys Res Commun. 1984 Nov 30;125(1):299–306. doi: 10.1016/s0006-291x(84)80368-x. [DOI] [PubMed] [Google Scholar]
  28. Knott T. J., Priestley L. M., Urdea M., Scott J. Isolation and characterisation of a cDNA encoding the precursor for human apolipoprotein AII. Biochem Biophys Res Commun. 1984 May 16;120(3):734–740. doi: 10.1016/s0006-291x(84)80168-0. [DOI] [PubMed] [Google Scholar]
  29. Knott T. J., Wallis S. C., Robertson M. E., Priestley L. M., Urdea M., Rall L. B., Scott J. The human apolipoprotein AII gene: structural organization and sites of expression. Nucleic Acids Res. 1985 Sep 11;13(17):6387–6398. doi: 10.1093/nar/13.17.6387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Krey G., Mahfoudi A., Wahli W. Functional interactions of peroxisome proliferator-activated receptor, retinoid-X receptor, and Sp1 in the transcriptional regulation of the acyl-coenzyme-A oxidase promoter. Mol Endocrinol. 1995 Feb;9(2):219–231. doi: 10.1210/mend.9.2.7776972. [DOI] [PubMed] [Google Scholar]
  31. 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 Oct 6;371(6497):528–531. doi: 10.1038/371528a0. [DOI] [PubMed] [Google Scholar]
  32. Kurokawa R., Söderström M., Hörlein A., Halachmi S., Brown M., Rosenfeld M. G., Glass C. K. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature. 1995 Oct 5;377(6548):451–454. doi: 10.1038/377451a0. [DOI] [PubMed] [Google Scholar]
  33. Laborda J. 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucleic Acids Res. 1991 Jul 25;19(14):3998–3998. doi: 10.1093/nar/19.14.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lackner K. J., Law S. W., Brewer H. B., Jr Human apolipoprotein A-II: complete nucleic acid sequence of preproapo A-II. FEBS Lett. 1984 Sep 17;175(1):159–164. doi: 10.1016/0014-5793(84)80590-6. [DOI] [PubMed] [Google Scholar]
  35. Lackner K. J., Law S. W., Brewer H. B., Jr, Sakaguchi A. Y., Naylor S. L. The human apolipoprotein A-II gene is located on chromosome 1. Biochem Biophys Res Commun. 1984 Aug 16;122(3):877–883. doi: 10.1016/0006-291x(84)91172-0. [DOI] [PubMed] [Google Scholar]
  36. Lackner K. J., Law S. W., Brewer H. B., Jr The human apolipoprotein A-II gene: complete nucleic acid sequence and genomic organization. Nucleic Acids Res. 1985 Jun 25;13(12):4597–4608. doi: 10.1093/nar/13.12.4597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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 HNF-4, ARP-1, EAR-2, and EAR-3. J Biol Chem. 1992 Aug 5;267(22):15849–15860. [PubMed] [Google Scholar]
  38. Lehmann J. M., Jong L., Fanjul A., Cameron J. F., Lu X. P., Haefner P., Dawson M. I., Pfahl M. Retinoids selective for retinoid X receptor response pathways. Science. 1992 Dec 18;258(5090):1944–1946. doi: 10.1126/science.1335166. [DOI] [PubMed] [Google Scholar]
  39. Leid M., Kastner P., Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci. 1992 Oct;17(10):427–433. doi: 10.1016/0968-0004(92)90014-z. [DOI] [PubMed] [Google Scholar]
  40. Leid M., Kastner P., Lyons R., Nakshatri H., Saunders M., Zacharewski T., Chen J. Y., Staub A., Garnier J. M., Mader S. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992 Jan 24;68(2):377–395. doi: 10.1016/0092-8674(92)90478-u. [DOI] [PubMed] [Google Scholar]
  41. Lucero M. A., Sanchez D., Ochoa A. R., Brunel F., Cohen G. N., Baralle F. E., Zakin M. M. Interaction of DNA-binding proteins with the tissue-specific human apolipoprotein-AII enhancer. Nucleic Acids Res. 1989 Mar 25;17(6):2283–2300. doi: 10.1093/nar/17.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lusis A. J., Taylor B. A., Wangenstein R. W., LeBoeuf R. C. Genetic control of lipid transport in mice. II. Genes controlling structure of high density lipoproteins. J Biol Chem. 1983 Apr 25;258(8):5071–5078. [PubMed] [Google Scholar]
  44. MacGregor G. R., Caskey C. T. Construction of plasmids that express E. coli beta-galactosidase in mammalian cells. Nucleic Acids Res. 1989 Mar 25;17(6):2365–2365. doi: 10.1093/nar/17.6.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mangelsdorf D. J., Ong E. S., Dyck J. A., Evans R. M. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990 May 17;345(6272):224–229. doi: 10.1038/345224a0. [DOI] [PubMed] [Google Scholar]
  46. Mangelsdorf D. J., Umesono K., Kliewer S. A., Borgmeyer U., Ong E. S., Evans R. M. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell. 1991 Aug 9;66(3):555–561. doi: 10.1016/0092-8674(81)90018-0. [DOI] [PubMed] [Google Scholar]
  47. Marsh J. L., Erfle M., Wykes E. J. The pIC plasmid and phage vectors with versatile cloning sites for recombinant selection by insertional inactivation. Gene. 1984 Dec;32(3):481–485. doi: 10.1016/0378-1119(84)90022-2. [DOI] [PubMed] [Google Scholar]
  48. Masiakowski P., Breathnach R., Bloch J., Gannon F., Krust A., Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982 Dec 20;10(24):7895–7903. doi: 10.1093/nar/10.24.7895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Mehrabian M., Qiao J. H., Hyman R., Ruddle D., Laughton C., Lusis A. J. Influence of the apoA-II gene locus on HDL levels and fatty streak development in mice. Arterioscler Thromb. 1993 Jan;13(1):1–10. doi: 10.1161/01.atv.13.1.1. [DOI] [PubMed] [Google Scholar]
  50. Moore M. N., Kao F. T., Tsao Y. K., Chan L. Human apolipoprotein A-II: nucleotide sequence of a cloned cDNA, and localization of its structural gene on human chromosome 1. Biochem Biophys Res Commun. 1984 Aug 30;123(1):1–7. doi: 10.1016/0006-291x(84)90371-1. [DOI] [PubMed] [Google Scholar]
  51. Perlmann T., Jansson L. A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev. 1995 Apr 1;9(7):769–782. doi: 10.1101/gad.9.7.769. [DOI] [PubMed] [Google Scholar]
  52. Perlmann T., Rangarajan P. N., Umesono K., Evans R. M. Determinants for selective RAR and TR recognition of direct repeat HREs. Genes Dev. 1993 Jul;7(7B):1411–1422. doi: 10.1101/gad.7.7b.1411. [DOI] [PubMed] [Google Scholar]
  53. Puchois P., Kandoussi A., Fievet P., Fourrier J. L., Bertrand M., Koren E., Fruchart J. C. Apolipoprotein A-I containing lipoproteins in coronary artery disease. Atherosclerosis. 1987 Nov;68(1-2):35–40. doi: 10.1016/0021-9150(87)90091-8. [DOI] [PubMed] [Google Scholar]
  54. Rottman J. N., Widom R. L., Nadal-Ginard B., Mahdavi V., Karathanasis S. K. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol. 1991 Jul;11(7):3814–3820. doi: 10.1128/mcb.11.7.3814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schonfeld G., Patsch W., Rudel L. L., Nelson C., Epstein M., Olson R. E. Effects of dietary cholesterol and fatty acids on plasma lipoproteins. J Clin Invest. 1982 May;69(5):1072–1080. doi: 10.1172/JCI110542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Schoonjans K., Watanabe M., Suzuki H., Mahfoudi A., Krey G., Wahli W., Grimaldi P., Staels B., Yamamoto T., Auwerx J. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem. 1995 Aug 18;270(33):19269–19276. doi: 10.1074/jbc.270.33.19269. [DOI] [PubMed] [Google Scholar]
  57. Schultz J. R., Verstuyft J. G., Gong E. L., Nichols A. V., Rubin E. M. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature. 1993 Oct 21;365(6448):762–764. doi: 10.1038/365762a0. [DOI] [PubMed] [Google Scholar]
  58. Sharpe C. R., Sidoli A., Shelley C. S., Lucero M. A., Shoulders C. C., Baralle F. E. Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance. Nucleic Acids Res. 1984 May 11;12(9):3917–3932. doi: 10.1093/nar/12.9.3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Shelley C. S., Baralle F. E. Dual tissue-specific expression of apo-AII is directed by an upstream enhancer. Nucleic Acids Res. 1987 May 11;15(9):3801–3821. doi: 10.1093/nar/15.9.3801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Shelley C. S., Sharpe C. R., Baralle F. E., Shoulders C. C. Comparison of the human apolipoprotein genes. Apo AII presents a unique functional intron-exon junction. J Mol Biol. 1985 Nov 5;186(1):43–51. doi: 10.1016/0022-2836(85)90255-4. [DOI] [PubMed] [Google Scholar]
  61. Takagi K., Strauss J. F., 3rd Control of low density lipoprotein receptor gene expression in steroidogenic cells. Can J Physiol Pharmacol. 1989 Aug;67(8):968–973. doi: 10.1139/y89-153. [DOI] [PubMed] [Google Scholar]
  62. Tora L., White J., Brou C., Tasset D., Webster N., Scheer E., Chambon P. The human estrogen receptor has two independent nonacidic transcriptional activation functions. Cell. 1989 Nov 3;59(3):477–487. doi: 10.1016/0092-8674(89)90031-7. [DOI] [PubMed] [Google Scholar]
  63. Tsai M. J., O'Malley B. W. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994;63:451–486. doi: 10.1146/annurev.bi.63.070194.002315. [DOI] [PubMed] [Google Scholar]
  64. Tsao Y. K., Wei C. F., Robberson D. L., Gotto A. M., Jr, Chan L. Isolation and characterization of the human apolipoprotein A-II gene. Electron microscopic analysis of RNA:DNA hybrids, nucleotide sequence, identification of a polymorphic MspI site, and general structural organization of apolipoprotein genes. J Biol Chem. 1985 Dec 5;260(28):15222–15231. [PubMed] [Google Scholar]
  65. Vanloo B., Taveirne J., Baert J., Lorent G., Lins L., Ruyschaert J. M., Rosseneu M. LCAT activation properties of apo A-I CNBr fragments and conversion of discoidal complexes into spherical particles. Biochim Biophys Acta. 1992 Oct 30;1128(2-3):258–266. doi: 10.1016/0005-2760(92)90316-n. [DOI] [PubMed] [Google Scholar]
  66. Vu-Dac N., Schoonjans K., Kosykh V., Dallongeville J., Fruchart J. C., Staels B., Auwerx J. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest. 1995 Aug;96(2):741–750. doi: 10.1172/JCI118118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Warden C. H., Hedrick C. C., Qiao J. H., Castellani L. W., Lusis A. J. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science. 1993 Jul 23;261(5120):469–472. doi: 10.1126/science.8332912. [DOI] [PubMed] [Google Scholar]
  68. Widom R. L., Rhee M., Karathanasis S. K. Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid. Mol Cell Biol. 1992 Aug;12(8):3380–3389. doi: 10.1128/mcb.12.8.3380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Willy P. J., Umesono K., Ong E. S., Evans R. M., Heyman R. A., Mangelsdorf D. J. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995 May 1;9(9):1033–1045. doi: 10.1101/gad.9.9.1033. [DOI] [PubMed] [Google Scholar]

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