Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 Jan 1;369(Pt 1):17–22. doi: 10.1042/BJ20021382

Hepatocyte nuclear factor-4 alpha mediates the stimulatory effect of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) on glucose-6-phosphatase catalytic subunit gene transcription in H4IIE cells.

Jared N Boustead 1, Beth T Stadelmaier 1, Angela M Eeds 1, Peter O Wiebe 1, Christina A Svitek 1, James K Oeser 1, Richard M O'Brien 1
PMCID: PMC1223073  PMID: 12416993

Abstract

It has recently been shown that adenoviral-mediated expression of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) in hepatocytes stimulates glucose-6-phosphatase catalytic subunit (G6Pase) gene expression. A combination of fusion gene, gel retardation and chromatin immunoprecipitation assays revealed that, in H4IIE cells, PGC-1 alpha mediates this stimulation through an evolutionarily conserved region of the G6Pase promoter that binds hepatocyte nuclear factor-4 alpha.

Full Text

The Full Text of this article is available as a PDF (149.8 KB).

Selected References

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

  1. Andersson U., Scarpulla R. C. Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol. 2001 Jun;21(11):3738–3749. doi: 10.1128/MCB.21.11.3738-3749.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews N. C., Faller D. V. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991 May 11;19(9):2499–2499. doi: 10.1093/nar/19.9.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aranda A., Pascual A. Nuclear hormone receptors and gene expression. Physiol Rev. 2001 Jul;81(3):1269–1304. doi: 10.1152/physrev.2001.81.3.1269. [DOI] [PubMed] [Google Scholar]
  4. Argaud D., Zhang Q., Pan W., Maitra S., Pilkis S. J., Lange A. J. Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states: gene structure and 5'-flanking sequence. Diabetes. 1996 Nov;45(11):1563–1571. doi: 10.2337/diab.45.11.1563. [DOI] [PubMed] [Google Scholar]
  5. Barzilai N., Rossetti L. Role of glucokinase and glucose-6-phosphatase in the acute and chronic regulation of hepatic glucose fluxes by insulin. J Biol Chem. 1993 Nov 25;268(33):25019–25025. [PubMed] [Google Scholar]
  6. Bennett M. K., Osborne T. F. Nutrient regulation of gene expression by the sterol regulatory element binding proteins: increased recruitment of gene-specific coregulatory factors and selective hyperacetylation of histone H3 in vivo. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6340–6344. doi: 10.1073/pnas.97.12.6340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Canuto R. A., Ferro M., Salvo R. A., Bassi A. M., Trombetta A., Maggiora M., Martinasso G., Lindahl R., Muzio G. Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells. Biochem J. 2001 Aug 1;357(Pt 3):811–818. doi: 10.1042/0264-6021:3570811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chapman S. C., Ayala J. E., Streeper R. S., Culbert A. A., Eaton E. M., Svitek C. A., Goldman J. K., Tavar J. M., O'Brien R. M. Multiple promoter elements are required for the stimulatory effect of insulin on human collagenase-1 gene transcription. Selective effects on activator protein-1 expression may explain the quantitative difference in insulin and phorbol ester action. J Biol Chem. 1999 Jun 25;274(26):18625–18634. doi: 10.1074/jbc.274.26.18625. [DOI] [PubMed] [Google Scholar]
  9. Cherrington A. D., Edgerton D., Sindelar D. K. The direct and indirect effects of insulin on hepatic glucose production in vivo. Diabetologia. 1998 Sep;41(9):987–996. doi: 10.1007/s001250051021. [DOI] [PubMed] [Google Scholar]
  10. Chou Janice Yang, Matern Dietrich, Mansfield Brian C., Chen Yuan-Tsong. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. Curr Mol Med. 2002 Mar;2(2):121–143. doi: 10.2174/1566524024605798. [DOI] [PubMed] [Google Scholar]
  11. Christ B., Nath A., Bastian H., Jungermann K. Regulation of the expression of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes by glucagon and insulin. Eur J Biochem. 1988 Dec 15;178(2):373–379. doi: 10.1111/j.1432-1033.1988.tb14460.x. [DOI] [PubMed] [Google Scholar]
  12. Desvergne B., Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999 Oct;20(5):649–688. doi: 10.1210/edrv.20.5.0380. [DOI] [PubMed] [Google Scholar]
  13. 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 Mar;16(3):925–931. doi: 10.1128/mcb.16.3.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Esterbauer H., Oberkofler H., Krempler F., Patsch W. Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics. 1999 Nov 15;62(1):98–102. doi: 10.1006/geno.1999.5977. [DOI] [PubMed] [Google Scholar]
  15. Galli A., Stewart M., Dorris R., Crabb D. High-level expression of RXRalpha and the presence of endogenous ligands contribute to expression of a peroxisome proliferator-activated receptor-responsive gene in hepatoma cells. Arch Biochem Biophys. 1998 Jun 15;354(2):288–294. doi: 10.1006/abbi.1997.0701. [DOI] [PubMed] [Google Scholar]
  16. Gerrish K., Cissell M. A., Stein R. The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. J Biol Chem. 2001 Oct 5;276(51):47775–47784. doi: 10.1074/jbc.M109244200. [DOI] [PubMed] [Google Scholar]
  17. Hara K., Tobe K., Okada T., Kadowaki H., Akanuma Y., Ito C., Kimura S., Kadowaki T. A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia. 2002 Apr 23;45(5):740–743. doi: 10.1007/s00125-002-0803-z. [DOI] [PubMed] [Google Scholar]
  18. Hayhurst G. P., Lee Y. H., Lambert G., Ward J. M., Gonzalez F. J. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 2001 Feb;21(4):1393–1403. doi: 10.1128/MCB.21.4.1393-1403.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herzig S., Long F., Jhala U. S., Hedrick S., Quinn R., Bauer A., Rudolph D., Schutz G., Yoon C., Puigserver P. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature. 2001 Sep 13;413(6852):179–183. doi: 10.1038/35093131. [DOI] [PubMed] [Google Scholar]
  20. Hutton J. C., Peshavaria M., Johnston C. F., Ravazzola M., Orci L. Immunolocalization of betagranin: a chromogranin A-related protein of the pancreatic B-cell. Endocrinology. 1988 Mar;122(3):1014–1020. doi: 10.1210/endo-122-3-1014. [DOI] [PubMed] [Google Scholar]
  21. Knutti D., Kaul A., Kralli A. A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen. Mol Cell Biol. 2000 Apr;20(7):2411–2422. doi: 10.1128/mcb.20.7.2411-2422.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Knutti D., Kralli A. PGC-1, a versatile coactivator. Trends Endocrinol Metab. 2001 Oct;12(8):360–365. doi: 10.1016/s1043-2760(01)00457-x. [DOI] [PubMed] [Google Scholar]
  23. Ktistaki E., Talianidis I. Modulation of hepatic gene expression by hepatocyte nuclear factor 1. Science. 1997 Jul 4;277(5322):109–112. doi: 10.1126/science.277.5322.109. [DOI] [PubMed] [Google Scholar]
  24. Kuo C. J., Conley P. B., Hsieh C. L., Francke U., Crabtree G. R. Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9838–9842. doi: 10.1073/pnas.87.24.9838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Li J., Ning G., Duncan S. A. Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev. 2000 Feb 15;14(4):464–474. [PMC free article] [PubMed] [Google Scholar]
  26. Lin B., Morris D. W., Chou J. Y. Hepatocyte nuclear factor 1alpha is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids. DNA Cell Biol. 1998 Nov;17(11):967–974. doi: 10.1089/dna.1998.17.967. [DOI] [PubMed] [Google Scholar]
  27. Lin Jiandie, Puigserver Pere, Donovan Jerry, Tarr Paul, Spiegelman Bruce M. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem. 2001 Nov 30;277(3):1645–1648. doi: 10.1074/jbc.C100631200. [DOI] [PubMed] [Google Scholar]
  28. Louet Jean-François, Hayhurst Graham, Gonzalez Frank J., Girard Jean, Decaux Jean-François. The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J Biol Chem. 2002 Jul 9;277(41):37991–38000. doi: 10.1074/jbc.M205087200. [DOI] [PubMed] [Google Scholar]
  29. Martin C. C., Oeser J. K., Svitek C. A., Hunter S. I., Hutton J. C., O'Brien R. M. Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. J Mol Endocrinol. 2002 Oct;29(2):205–222. doi: 10.1677/jme.0.0290205. [DOI] [PubMed] [Google Scholar]
  30. Marzluff W. F. Preparation of active nuclei. Methods Enzymol. 1990;181:30–36. doi: 10.1016/0076-6879(90)81109-8. [DOI] [PubMed] [Google Scholar]
  31. Miquerol L., Lopez S., Cartier N., Tulliez M., Raymondjean M., Kahn A. Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4 transcription factor in exocrine and endocrine pancreas. J Biol Chem. 1994 Mar 25;269(12):8944–8951. [PubMed] [Google Scholar]
  32. O'Brien R. M., Printz R. L., Halmi N., Tiesinga J. J., Granner D. K. Structural and functional analysis of the human phosphoenolpyruvate carboxykinase gene promoter. Biochim Biophys Acta. 1995 Dec 27;1264(3):284–288. doi: 10.1016/0167-4781(95)00194-8. [DOI] [PubMed] [Google Scholar]
  33. Orlando V. Mapping chromosomal proteins in vivo by formaldehyde-crosslinked-chromatin immunoprecipitation. Trends Biochem Sci. 2000 Mar;25(3):99–104. doi: 10.1016/s0968-0004(99)01535-2. [DOI] [PubMed] [Google Scholar]
  34. Orlando V., Strutt H., Paro R. Analysis of chromatin structure by in vivo formaldehyde cross-linking. Methods. 1997 Feb;11(2):205–214. doi: 10.1006/meth.1996.0407. [DOI] [PubMed] [Google Scholar]
  35. Puigserver P., Wu Z., Park C. W., Graves R., Wright M., Spiegelman B. M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998 Mar 20;92(6):829–839. doi: 10.1016/s0092-8674(00)81410-5. [DOI] [PubMed] [Google Scholar]
  36. Ryffel G. U. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. J Mol Endocrinol. 2001 Aug;27(1):11–29. doi: 10.1677/jme.0.0270011. [DOI] [PubMed] [Google Scholar]
  37. Sasaki K., Cripe T. P., Koch S. R., Andreone T. L., Petersen D. D., Beale E. G., Granner D. K. Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. J Biol Chem. 1984 Dec 25;259(24):15242–15251. [PubMed] [Google Scholar]
  38. Schmoll D., Allan B. B., Burchell A. Cloning and sequencing of the 5' region of the human glucose-6-phosphatase gene: transcriptional regulation by cAMP, insulin and glucocorticoids in H4IIE hepatoma cells. FEBS Lett. 1996 Mar 25;383(1-2):63–66. doi: 10.1016/0014-5793(96)00224-4. [DOI] [PubMed] [Google Scholar]
  39. Shih D. Q., Stoffel M. Dissecting the transcriptional network of pancreatic islets during development and differentiation. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14189–14191. doi: 10.1073/pnas.251558998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Streeper R. S., Eaton E. M., Ebert D. H., Chapman S. C., Svitek C. A., O'Brien R. M. Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9208–9213. doi: 10.1073/pnas.95.16.9208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Streeper R. S., Svitek C. A., Chapman S., Greenbaum L. E., Taub R., O'Brien R. M. A multicomponent insulin response sequence mediates a strong repression of mouse glucose-6-phosphatase gene transcription by insulin. J Biol Chem. 1997 May 2;272(18):11698–11701. doi: 10.1074/jbc.272.18.11698. [DOI] [PubMed] [Google Scholar]
  43. Streeper R. S., Svitek C. A., Goldman J. K., O'Brien R. M. Differential role of hepatocyte nuclear factor-1 in the regulation of glucose-6-phosphatase catalytic subunit gene transcription by cAMP in liver- and kidney-derived cell lines. J Biol Chem. 2000 Apr 21;275(16):12108–12118. doi: 10.1074/jbc.275.16.12108. [DOI] [PubMed] [Google Scholar]
  44. Vega R. B., Huss J. M., Kelly D. P. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol. 2000 Mar;20(5):1868–1876. doi: 10.1128/mcb.20.5.1868-1876.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Yoon J. C., Puigserver P., Chen G., Donovan J., Wu Z., Rhee J., Adelmant G., Stafford J., Kahn C. R., Granner D. K. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001 Sep 13;413(6852):131–138. doi: 10.1038/35093050. [DOI] [PubMed] [Google Scholar]
  46. van Schaftingen Emile, Gerin Isabelle. The glucose-6-phosphatase system. Biochem J. 2002 Mar 15;362(Pt 3):513–532. doi: 10.1042/0264-6021:3620513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. van de Werve G., Lange A., Newgard C., Méchin M. C., Li Y., Berteloot A. New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system. Eur J Biochem. 2000 Mar;267(6):1533–1549. doi: 10.1046/j.1432-1327.2000.01160.x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES