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. 1994 Nov;14(11):7124–7133. doi: 10.1128/mcb.14.11.7124

Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors.

O Yanuka-Kashles 1, H Cohen 1, M Trus 1, A Aran 1, N Benvenisty 1, L Reshef 1
PMCID: PMC359246  PMID: 7935427

Abstract

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however, Hepa cells failed to express the early-expressed factors hepatocyte nuclear factor 1 alpha (HNF-1 alpha) and HNF-4 and the late-expressed factor C/EBP alpha, thereby providing a suitable system for examining possible cooperation between these factors in the transcriptional regulation of the PEPCK gene. Transient transfection assays of a chimeric PEPCK-chloramphenicol acetyltransferase construct showed a residual PEPCK promoter activity in the Hepa cell line, which was slightly stimulated by cotransfection with a single transcription factor from either the C/EBP family or HNF-1 alpha but not at all affected by cotransfection of HNF-4. In contrast, cotransfection of the PEPCK construct with members from the C/EBP family plus HNF-1 alpha resulted in a synergistic stimulation of the PEPCK promoter activity. This synergistic effect depended on the presence in the PEPCK promoter region of the HNF-1 recognition sequence and on the presence of two C/EBP recognition sequences. The results demonstrate a requirement for coexistence and cooperation between early and late liver-enriched transcription factors in the transcriptional regulation of the PEPCK gene. In addition, the results suggest redundancy between members of the C/EBP family of transcription factors in the regulation of PEPCK gene expression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ang S. L., Wierda A., Wong D., Stevens K. A., Cascio S., Rossant J., Zaret K. S. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993 Dec;119(4):1301–1315. doi: 10.1242/dev.119.4.1301. [DOI] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benvenisty N., Nechushtan H., Cohen H., Reshef L. Separate cis-regulatory elements confer expression of phosphoenolpyruvate carboxykinase (GTP) gene in different cell lines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1118–1122. doi: 10.1073/pnas.86.4.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benvenisty N., Reshef L. Developmental acquisition of DNase I sensitivity of the phosphoenolpyruvate carboxykinase (GTP) gene in rat liver. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1132–1136. doi: 10.1073/pnas.84.5.1132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birkenmeier E. H., Gwynn B., Howard S., Jerry J., Gordon J. I., Landschulz W. H., McKnight S. L. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 1989 Aug;3(8):1146–1156. doi: 10.1101/gad.3.8.1146. [DOI] [PubMed] [Google Scholar]
  6. Blumenfeld M., Maury M., Chouard T., Yaniv M., Condamine H. Hepatic nuclear factor 1 (HNF1) shows a wider distribution than products of its known target genes in developing mouse. Development. 1991 Oct;113(2):589–599. doi: 10.1242/dev.113.2.589. [DOI] [PubMed] [Google Scholar]
  7. Bokar J. A., Roesler W. J., Vandenbark G. R., Kaetzel D. M., Hanson R. W., Nilson J. H. Characterization of the cAMP responsive elements from the genes for the alpha-subunit of glycoprotein hormones and phosphoenolpyruvate carboxykinase (GTP). Conserved features of nuclear protein binding between tissues and species. J Biol Chem. 1988 Dec 25;263(36):19740–19747. [PubMed] [Google Scholar]
  8. Boshart M., Weih F., Nichols M., Schütz G. The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase. Cell. 1991 Sep 6;66(5):849–859. doi: 10.1016/0092-8674(91)90432-x. [DOI] [PubMed] [Google Scholar]
  9. Cascio S., Zaret K. S. Hepatocyte differentiation initiates during endodermal-mesenchymal interactions prior to liver formation. Development. 1991 Sep;113(1):217–225. doi: 10.1242/dev.113.1.217. [DOI] [PubMed] [Google Scholar]
  10. Cereghini S., Ott M. O., Power S., Maury M. Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles. Development. 1992 Nov;116(3):783–797. doi: 10.1242/dev.116.3.783. [DOI] [PubMed] [Google Scholar]
  11. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  13. Darlington G. J. Liver cell lines. Methods Enzymol. 1987;151:19–38. doi: 10.1016/s0076-6879(87)51006-0. [DOI] [PubMed] [Google Scholar]
  14. De Simone V., Cortese R. Transcriptional regulation of liver-specific gene expression. Curr Opin Cell Biol. 1991 Dec;3(6):960–965. doi: 10.1016/0955-0674(91)90114-e. [DOI] [PubMed] [Google Scholar]
  15. DeFranco D., Bali D., Torres R., DePinho R. A., Erickson R. P., Gluecksohn-Waelsch S. The glucocorticoid hormone signal transduction pathway in mice homozygous for chromosomal deletions causing failure of cell type-specific inducible gene expression. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5607–5610. doi: 10.1073/pnas.88.13.5607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Descombes P., Schibler U. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell. 1991 Nov 1;67(3):569–579. doi: 10.1016/0092-8674(91)90531-3. [DOI] [PubMed] [Google Scholar]
  17. Eisenberger C. L., Nechushtan H., Cohen H., Shani M., Reshef L. Differential regulation of the rat phosphoenolpyruvate carboxykinase gene expression in several tissues of transgenic mice. Mol Cell Biol. 1992 Mar;12(3):1396–1403. doi: 10.1128/mcb.12.3.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gluecksohn-Waelsch S. Genetic control of morphogenetic and biochemical differentiation: lethal albino deletions in the mouse. Cell. 1979 Feb;16(2):225–237. doi: 10.1016/0092-8674(79)90001-1. [DOI] [PubMed] [Google Scholar]
  19. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gorski K., Carneiro M., Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell. 1986 Dec 5;47(5):767–776. doi: 10.1016/0092-8674(86)90519-2. [DOI] [PubMed] [Google Scholar]
  21. Hall R. K., Scott D. K., Noisin E. L., Lucas P. C., Granner D. K. Activation of the phosphoenolpyruvate carboxykinase gene retinoic acid response element is dependent on a retinoic acid receptor/coregulator complex. Mol Cell Biol. 1992 Dec;12(12):5527–5535. doi: 10.1128/mcb.12.12.5527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hankinson O. Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci U S A. 1979 Jan;76(1):373–376. doi: 10.1073/pnas.76.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  24. Hod Y., Cook J. S., Weldon S. L., Short J. M., Wynshaw-Boris A., Hanson R. W. Differential expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase. Ann N Y Acad Sci. 1986;478:31–45. doi: 10.1111/j.1749-6632.1986.tb15519.x. [DOI] [PubMed] [Google Scholar]
  25. Hoodless P. A., Roy R. N., Ryan A. K., Haché R. J., Vasa M. Z., Deeley R. G. Developmental regulation of specific protein interactions with an enhancerlike binding site far upstream from the avian very-low-density apolipoprotein II gene. Mol Cell Biol. 1990 Jan;10(1):154–164. doi: 10.1128/mcb.10.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Imai E., Miner J. N., Mitchell J. A., Yamamoto K. R., Granner D. K. Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. J Biol Chem. 1993 Mar 15;268(8):5353–5356. [PubMed] [Google Scholar]
  27. Imai E., Stromstedt P. E., Quinn P. G., Carlstedt-Duke J., Gustafsson J. A., Granner D. K. Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1990 Sep;10(9):4712–4719. doi: 10.1128/mcb.10.9.4712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ingram R. S., Scott R. W., Tilghman S. M. alpha-Fetoprotein and albumin genes are in tandem in the mouse genome. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4694–4698. doi: 10.1073/pnas.78.8.4694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Jones K. W., Shapero M. H., Chevrette M., Fournier R. E. Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A. Cell. 1991 Sep 6;66(5):861–872. doi: 10.1016/0092-8674(91)90433-y. [DOI] [PubMed] [Google Scholar]
  30. Kioussis D., Hamilton R., Hanson R. W., Tilghman S. M., Taylor J. M. Construction and cloning of rat albumin structural gene sequences. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4370–4374. doi: 10.1073/pnas.76.9.4370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
  32. Lai E., Darnell J. E., Jr Transcriptional control in hepatocytes: a window on development. Trends Biochem Sci. 1991 Nov;16(11):427–430. doi: 10.1016/0968-0004(91)90169-v. [DOI] [PubMed] [Google Scholar]
  33. Lassar A. B., Davis R. L., Wright W. E., Kadesch T., Murre C., Voronova A., Baltimore D., Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. doi: 10.1016/0092-8674(91)90620-e. [DOI] [PubMed] [Google Scholar]
  34. Levy S., Avni D., Hariharan N., Perry R. P., Meyuhas O. Oligopyrimidine tract at the 5' end of mammalian ribosomal protein mRNAs is required for their translational control. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3319–3323. doi: 10.1073/pnas.88.8.3319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Liu J. S., Park E. A., Gurney A. L., Roesler W. J., Hanson R. W. Cyclic AMP induction of phosphoenolpyruvate carboxykinase (GTP) gene transcription is mediated by multiple promoter elements. J Biol Chem. 1991 Oct 5;266(28):19095–19102. [PubMed] [Google Scholar]
  36. Lucas P. C., Forman B. M., Samuels H. H., Granner D. K. Specificity of a retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter: consequences of both retinoic acid and thyroid hormone receptor binding. Mol Cell Biol. 1991 Oct;11(10):5164–5170. doi: 10.1128/mcb.11.10.5164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Metzger S., Halaas J. L., Breslow J. L., Sladek F. M. Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription. J Biol Chem. 1993 Aug 5;268(22):16831–16838. [PubMed] [Google Scholar]
  38. Mietus-Snyder M., Sladek F. M., Ginsburg G. S., Kuo C. F., Ladias J. A., Darnell J. E., Jr, 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 Apr;12(4):1708–1718. doi: 10.1128/mcb.12.4.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nishiyori A., Tashiro H., Kimura A., Akagi K., Yamamura K., Mori M., Takiguchi M. Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors. Both HNF-4 and C/EBP beta are required for liver-specific activity of the ornithine transcarbamylase enhancer. J Biol Chem. 1994 Jan 14;269(2):1323–1331. [PubMed] [Google Scholar]
  40. O'Brien R. M., Lucas P. C., Forest C. D., Magnuson M. A., Granner D. K. Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. Science. 1990 Aug 3;249(4968):533–537. doi: 10.1126/science.2166335. [DOI] [PubMed] [Google Scholar]
  41. PITOT H. C., PERAINO C., MORSE P. A., Jr, POTTER V. R. HEPATOMAS IN TISSUE CULTURE COMPARED WITH ADAPTING LIVER IN VIVO. Natl Cancer Inst Monogr. 1964 Apr;13:229–245. [PubMed] [Google Scholar]
  42. Pani L., Overdier D. G., Porcella A., Qian X., Lai E., Costa R. H. Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein. Mol Cell Biol. 1992 Sep;12(9):3723–3732. doi: 10.1128/mcb.12.9.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Park E. A., Gurney A. L., Nizielski S. E., Hakimi P., Cao Z., Moorman A., Hanson R. W. Relative roles of CCAAT/enhancer-binding protein beta and cAMP regulatory element-binding protein in controlling transcription of the gene for phosphoenolpyruvate carboxykinase (GTP). J Biol Chem. 1993 Jan 5;268(1):613–619. [PubMed] [Google Scholar]
  44. Park E. A., Roesler W. J., Liu J., Klemm D. J., Gurney A. L., Thatcher J. D., Shuman J., Friedman A., Hanson R. W. The role of the CCAAT/enhancer-binding protein in the transcriptional regulation of the gene for phosphoenolpyruvate carboxykinase (GTP). Mol Cell Biol. 1990 Dec;10(12):6264–6272. doi: 10.1128/mcb.10.12.6264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Powell D. J., Friedman J. M., Oulette A. J., Krauter K. S., Darnell J. E., Jr Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver. J Mol Biol. 1984 Oct 15;179(1):21–35. doi: 10.1016/0022-2836(84)90304-8. [DOI] [PubMed] [Google Scholar]
  46. Quinn P. G., Wong T. W., Magnuson M. A., Shabb J. B., Granner D. K. Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1988 Aug;8(8):3467–3475. doi: 10.1128/mcb.8.8.3467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rey-Campos J., Chouard T., Yaniv M., Cereghini S. vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1. EMBO J. 1991 Jun;10(6):1445–1457. doi: 10.1002/j.1460-2075.1991.tb07665.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Roesler W. J., McFie P. J., Puttick D. M. Evidence for the involvement of at least two distinct transcription factors, one of which is liver-enriched, for the activation of the phosphoenolpyruvate carboxykinase gene promoter by cAMP. J Biol Chem. 1993 Feb 15;268(5):3791–3796. [PubMed] [Google Scholar]
  49. Roesler W. J., Vandenbark G. R., Hanson R. W. Identification of multiple protein binding domains in the promoter-regulatory region of the phosphoenolpyruvate carboxykinase (GTP) gene. J Biol Chem. 1989 Jun 5;264(16):9657–9664. [PubMed] [Google Scholar]
  50. Ron D., Habener J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992 Mar;6(3):439–453. doi: 10.1101/gad.6.3.439. [DOI] [PubMed] [Google Scholar]
  51. Rudnicki M. A., Braun T., Hinuma S., Jaenisch R. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell. 1992 Oct 30;71(3):383–390. doi: 10.1016/0092-8674(92)90508-a. [DOI] [PubMed] [Google Scholar]
  52. Rudnicki M. A., Schnegelsberg P. N., Stead R. H., Braun T., Arnold H. H., Jaenisch R. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell. 1993 Dec 31;75(7):1351–1359. doi: 10.1016/0092-8674(93)90621-v. [DOI] [PubMed] [Google Scholar]
  53. Ruppert S., Boshart M., Bosch F. X., Schmid W., Fournier R. E., Schütz G. Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes. Cell. 1990 Jun 1;61(5):895–904. doi: 10.1016/0092-8674(90)90200-x. [DOI] [PubMed] [Google Scholar]
  54. Schafer A. J., Fournier R. E. Multiple elements regulate phosphoenolpyruvate carboxykinase gene expression in hepatoma hybrid cells. Somat Cell Mol Genet. 1992 Nov;18(6):571–581. doi: 10.1007/BF01232653. [DOI] [PubMed] [Google Scholar]
  55. Short J. M., Wynshaw-Boris A., Short H. P., Hanson R. W. Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. II. Identification of cAMP and glucocorticoid regulatory domains. J Biol Chem. 1986 Jul 25;261(21):9721–9726. [PubMed] [Google Scholar]
  56. Short M. K., Clouthier D. E., Schaefer I. M., Hammer R. E., Magnuson M. A., Beale E. G. Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice. Mol Cell Biol. 1992 Mar;12(3):1007–1020. doi: 10.1128/mcb.12.3.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Shoshani T., Benvenisty N., Trus M., Reshef L. Cis-regulatory elements that confer differential expression upon the rat gene encoding phosphoenolpyruvate carboxykinase in kidney and liver. Gene. 1991 May 30;101(2):279–283. doi: 10.1016/0378-1119(91)90424-a. [DOI] [PubMed] [Google Scholar]
  58. Sladek F. M., Zhong W. M., Lai E., Darnell J. E., Jr Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990 Dec;4(12B):2353–2365. doi: 10.1101/gad.4.12b.2353. [DOI] [PubMed] [Google Scholar]
  59. Thayer M. J., Lugo T. G., Leach R. J., Fournier R. E. Regulation of chimeric phosphoenolpyruvate carboxykinase genes by the trans-dominant locus TSE1. Mol Cell Biol. 1990 Jun;10(6):2660–2668. doi: 10.1128/mcb.10.6.2660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Tilghman S. M., Belayew A. Transcriptional control of the murine albumin/alpha-fetoprotein locus during development. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5254–5257. doi: 10.1073/pnas.79.17.5254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tilghman S. M., Kioussis D., Gorin M. B., Ruiz J. P., Ingram R. S. The presence of intervening sequences in the alpha-fetoprotein gene of the mouse. J Biol Chem. 1979 Aug 10;254(15):7393–7399. [PubMed] [Google Scholar]
  62. Toniatti C., Demartis A., Monaci P., Nicosia A., Ciliberto G. Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. EMBO J. 1990 Dec;9(13):4467–4475. doi: 10.1002/j.1460-2075.1990.tb07897.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Trus M., Benvenisty N., Cohen H., Reshef L. Developmentally regulated interactions of liver nuclear factors with the rat phosphoenolpyruvate carboxykinase promoter. Mol Cell Biol. 1990 May;10(5):2418–2422. doi: 10.1128/mcb.10.5.2418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Tsutsumi K., Ito K., Ishikawa K. Developmental appearance of transcription factors that regulate liver-specific expression of the aldolase B gene. Mol Cell Biol. 1989 Nov;9(11):4923–4931. doi: 10.1128/mcb.9.11.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wu K. J., Wilson D. R., Shih C., Darlington G. J. The transcription factor HNF1 acts with C/EBP alpha to synergistically activate the human albumin promoter through a novel domain. J Biol Chem. 1994 Jan 14;269(2):1177–1182. [PubMed] [Google Scholar]
  67. Yoo-Warren H., Monahan J. E., Short J., Short H., Bruzel A., Wynshaw-Boris A., Meisner H. M., Samols D., Hanson R. W. Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3656–3660. doi: 10.1073/pnas.80.12.3656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. el-Maghrabi M. R., Pilkis J., Marker A. J., Colosia A. D., D'Angelo G., Fraser B. A., Pilkis S. J. cDNA sequence of rat liver fructose-1,6-bisphosphatase and evidence for down-regulation of its mRNA by insulin. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8430–8434. doi: 10.1073/pnas.85.22.8430. [DOI] [PMC free article] [PubMed] [Google Scholar]

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