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. 1997 Sep 1;326(Pt 2):587–592. doi: 10.1042/bj3260587

Chicken ovalbumin upstream-promoter transcription factor (COUP-TF) could act as a transcriptional activator or repressor of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene.

J C Rodríguez 1, J A Ortiz 1, F G Hegardt 1, D Haro 1
PMCID: PMC1218709  PMID: 9291136

Abstract

The chicken ovalbumin upstream-promoter transcription factor (COUP-TF) has a dual effect on the regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene. COUP-TF could act as a transcriptional activator or repressor of this gene through different DNA sequences. COUP-TF induces expression of a reporter gene linked to the mitochondrial HMG-CoA synthase gene promoter in human hepatoma HepG2 cells, but represses it in a Leydig tumour cell line (R2C); in both these cell lines the expression of the mitochondrial HMG-CoA synthase gene mimics that of liver and testis. The activation is promoted by a fragment of the gene from coordinates -62 to +28, which contains a GC box and a TATA box, and where no COUP-TF binding site was observed by in vitro DNA binding studies. On the other hand, the COUP-TF inhibitory effect is mainly due to repression of peroxisome-proliferator-activated receptor-dependent activation of the gene, interacting with the region from -104 to -92. To our knowledge this work represents the second example of a target gene for COUP-TF I that could be either activated or repressed by the action of this receptor through different DNA sequences of the same gene.

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Selected References

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

  1. Baes M., Castelein H., Desmet L., Declercq P. E. Antagonism of COUP-TF and PPAR alpha/RXR alpha on the activation of the malic enzyme gene promoter: modulation by 9-cis RA. Biochem Biophys Res Commun. 1995 Oct 4;215(1):338–345. doi: 10.1006/bbrc.1995.2471. [DOI] [PubMed] [Google Scholar]
  2. Berrodin T. J., Marks M. S., Ozato K., Linney E., Lazar M. A. Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein. Mol Endocrinol. 1992 Sep;6(9):1468–1478. doi: 10.1210/mend.6.9.1331778. [DOI] [PubMed] [Google Scholar]
  3. Bocos C., Göttlicher M., Gearing K., Banner C., Enmark E., Teboul M., Crickmore A., Gustafsson J. A. Fatty acid activation of peroxisome proliferator-activated receptor (PPAR). J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):467–473. doi: 10.1016/0960-0760(95)00093-f. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Casals N., Roca N., Guerrero M., Gil-Gómez G., Ayté J., Ciudad C. J., Hegardt F. G. Regulation of the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene. Its role in the control of ketogenesis. Biochem J. 1992 Apr 1;283(Pt 1):261–264. doi: 10.1042/bj2830261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  7. 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 Feb 25;268(6):4152–4160. [PubMed] [Google Scholar]
  8. Cooney A. J., Tsai S. Y., O'Malley B. W., Tsai M. J. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol Cell Biol. 1992 Sep;12(9):4153–4163. doi: 10.1128/mcb.12.9.4153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaudet F., Ginsburg G. S. Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1. J Biol Chem. 1995 Dec 15;270(50):29916–29922. doi: 10.1074/jbc.270.50.29916. [DOI] [PubMed] [Google Scholar]
  10. Gil-Gómez G., Ayté J., Hegardt F. G. The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity. Eur J Biochem. 1993 Apr 15;213(2):773–779. doi: 10.1111/j.1432-1033.1993.tb17819.x. [DOI] [PubMed] [Google Scholar]
  11. Green S., Wahli W. Peroxisome proliferator-activated receptors: finding the orphan a home. Mol Cell Endocrinol. 1994 Apr;100(1-2):149–153. doi: 10.1016/0303-7207(94)90294-1. [DOI] [PubMed] [Google Scholar]
  12. Hwung Y. P., Crowe D. T., Wang L. H., Tsai S. Y., Tsai M. J. The COUP transcription factor binds to an upstream promoter element of the rat insulin II gene. Mol Cell Biol. 1988 May;8(5):2070–2077. doi: 10.1128/mcb.8.5.2070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  14. Ing N. H., Beekman J. M., Tsai S. Y., Tsai M. J., O'Malley B. W. Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). J Biol Chem. 1992 Sep 5;267(25):17617–17623. [PubMed] [Google Scholar]
  15. Kadowaki Y., Toyoshima K., Yamamoto T. Dual transcriptional control by Ear3/COUP: negative regulation through the DR1 direct repeat and positive regulation through a sequence downstream of the transcriptional start site of the mouse mammary tumor virus promoter. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4432–4436. doi: 10.1073/pnas.92.10.4432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kimura A., Nishiyori A., Murakami T., Tsukamoto T., Hata S., Osumi T., Okamura R., Mori M., Takiguchi M. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4). J Biol Chem. 1993 May 25;268(15):11125–11133. [PubMed] [Google Scholar]
  17. Kliewer S. A., Umesono K., Heyman R. A., Mangelsdorf D. J., Dyck J. A., Evans R. M. Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1448–1452. doi: 10.1073/pnas.89.4.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Legraverend C., Eguchi H., Ström A., Lahuna O., Mode A., Tollet P., Westin S., Gustafsson J. A. Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily. Biochemistry. 1994 Aug 23;33(33):9889–9897. doi: 10.1021/bi00199a010. [DOI] [PubMed] [Google Scholar]
  20. Malik S., Karathanasis S. Transcriptional activation by the orphan nuclear receptor ARP-1. Nucleic Acids Res. 1995 May 11;23(9):1536–1543. doi: 10.1093/nar/23.9.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miyata K. S., Zhang B., Marcus S. L., Capone J. P., Rachubinski R. A. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling. J Biol Chem. 1993 Sep 15;268(26):19169–19172. [PubMed] [Google Scholar]
  22. Palmer C. N., Hsu M. H., Muerhoff A. S., Griffin K. J., Johnson E. F. Interaction of the peroxisome proliferator-activated receptor alpha with the retinoid X receptor alpha unmasks a cryptic peroxisome proliferator response element that overlaps an ARP-1-binding site in the CYP4A6 promoter. J Biol Chem. 1994 Jul 8;269(27):18083–18089. [PubMed] [Google Scholar]
  23. 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 Aug;6(8):2784–2791. doi: 10.1128/mcb.6.8.2784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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 Mar;16(3):778–791. doi: 10.1128/mcb.16.3.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rodríguez J. C., Gil-Gómez G., Hegardt F. G., Haro D. Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. J Biol Chem. 1994 Jul 22;269(29):18767–18772. [PubMed] [Google Scholar]
  26. 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 Dec;6(12):4259–4267. doi: 10.1128/mcb.6.12.4259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schaeffer E., Guillou F., Part D., Zakin M. M. A different combination of transcription factors modulates the expression of the human transferrin promoter in liver and Sertoli cells. J Biol Chem. 1993 Nov 5;268(31):23399–23408. [PubMed] [Google Scholar]
  28. Tong G. X., Tanen M. R., Bagchi M. K. Ligand modulates the interaction of thyroid hormone receptor beta with the basal transcription machinery. J Biol Chem. 1995 May 5;270(18):10601–10611. doi: 10.1074/jbc.270.18.10601. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Tsai S. Y., Sagami I., Wang H., Tsai M. J., O'Malley B. W. Interactions between a DNA-binding transcription factor (COUP) and a non-DNA binding factor (S300-II). Cell. 1987 Aug 28;50(5):701–709. doi: 10.1016/0092-8674(87)90328-x. [DOI] [PubMed] [Google Scholar]

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