Distinct Repressive Properties of the Mammalian and Fish Orphan Nuclear Receptors SHP and DAX-1

  • Park, Yun-Yong (Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University) ;
  • Teyssier, Catherine (Genotypes et Phenotypes Tumoraux, INSERM EMI 229, Centre Regional de Lutte contre le Cancer) ;
  • Vanacker, Jean-Marc (Genotypes et Phenotypes Tumoraux, INSERM EMI 229, Centre Regional de Lutte contre le Cancer) ;
  • Choi, Hueng-Sik (Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University)
  • Received : 2006.12.05
  • Accepted : 2007.03.02
  • Published : 2007.06.30

Abstract

It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1 (nDAX-1/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1, although the physical interaction with human SF-1 was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

Keywords

Acknowledgement

Supported by : National Research Laboratory, KRF

References

  1. Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 2185-2195 https://doi.org/10.1126/science.287.5461.2185
  2. Altincicek, B., Tenbaum, S. P., Dressel, U., Thormeyer, D., Renkawitz, R., et al. (2000) Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenital. J. Biol. Chem. 275, 7662-7667 https://doi.org/10.1074/jbc.275.11.7662
  3. Bardet, P. L., Horard, B., Robinson-Rechavi, M., Laudet, V., and Vanacker, J. M. (2002) Characterization of estrogen receptors in zebrafish (Danio rerio). J. Mol. Endo. 28, 153-163 https://doi.org/10.1677/jme.0.0280153
  4. Bardet, P. L., Obrecht-Pflumio, S., Thisse, C., Laudet, V., Thisse, B., et al. (2004) Cloning and developmental expression of five estrogen-receptor related genes in the zebrafish. Dev. Genes Evol. 214, 240-249 https://doi.org/10.1007/s00427-004-0404-6
  5. Bavner, A., Johansson, L., Toresson, G., Gustafsson, J. A., and Treuter, E. (2002) A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP. EMBO Rep. 3, 478-484 https://doi.org/10.1093/embo-reports/kvf087
  6. Beuschlein, F., Keegan, C. E., Bavers, D. L., Mutch, C., Hutz, J. E., et al. (2002) SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis. Endocr. Res. 28, 597-607 https://doi.org/10.1081/ERC-120016972
  7. Crawford, P. A., Dorn, C., Sadovsky, Y., and Milbrandt, J. (1998) Nuclear receptor DAX-1 recruits nuclear receptor corepressor N-CoR to steroidogenic factor 1. Mol. Cell. Biol. 18, 2949-2956 https://doi.org/10.1128/MCB.18.5.2949
  8. Escriva, H., Bertrand, S., and Laudet, V. (2004) The evolution of the nuclear receptor superfamily. Essays Biochem. 40, 11-26 https://doi.org/10.1042/bse0400011
  9. Giguere, V. (1999) Orphan nuclear receptors: from gene to function. Endocr. Rev. 20, 689-725 https://doi.org/10.1210/er.20.5.689
  10. Gobinet, J., Auzou, G., Nicolas, J. C., Sultan, C., and Jalaguier, S. (2001) Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP. Biochemistry 40, 15369-15377 https://doi.org/10.1021/bi011384o
  11. Goodwin, B., Jones, S. A., Price, R. R., Watson, M. A., McKee, D. D., et al. (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6, 517-526 https://doi.org/10.1016/S1097-2765(00)00051-4
  12. Holter, E., Kotaja, N., Makela, S., Strauss, L., Kietz, S., et al. (2002) Inhibition of Androgen Receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Mol. Endocrinol. 16, 515-528 https://doi.org/10.1210/me.16.3.515
  13. Ito, M., Yu, R., and Jameson, J. L. (1997) DAX-1 inhibits SF-1- mediated transactivation via a carboxy-terminal domain that is deleted in adrenal hypoplasia congenital. Mol. Cell. Biol. 17, 1476-1483 https://doi.org/10.1128/MCB.17.3.1476
  14. Johansson, L., Thomsen, J. S., Damdimopoulos, A. E., Spyrou, G., Gustafsson, J. A., et al. (1999) The orphan nuclear receptor SHP inhibits agonist-dependent transcriptional activity of estrogen receptors ER$\alpha$ and ER$\beta$ J. Biol. Chem. 274, 345-353 https://doi.org/10.1074/jbc.274.1.345
  15. Johansson, L., Bavner, A., Thomsen, J. S., Farnegardh, M., Gustafsson, J. A., et al. (2000) The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated Estrogen Receptors. Mol. Cell. Biol. 20, 1124-1133 https://doi.org/10.1128/MCB.20.4.1124-1133.2000
  16. Kawajiri, K., Ikuta, T., Suzuki, T., Kusaka, M., Muramatsu, M., et al. (2003) Role of the LXXLL-motif and activation function 2 domain in subcellular localization of Dax-1 (dosagesensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1). Mol. Endocrinol. 17, 994-1004 https://doi.org/10.1210/me.2002-0360
  17. Kemper, J. K., Kim, H., Miao, J., Bhalla, S., and Bae, Y. (2004) Role of an mSin3A-Swi/Snf chromatin remodeling complex in the feedback repression of bile acid biosynthesis by SHP. Mol. Cell. Biol. 24, 7707-7719 https://doi.org/10.1128/MCB.24.17.7707-7719.2004
  18. Kim, H. J., Lee, S. K., Na, S. Y., Choi, H. S., and Lee, J. W. (1998) Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2. Mol. Endocrinol. 12, 1038-1047 https://doi.org/10.1210/me.12.7.1038
  19. Kim, J. Y., Chu, K., Kim, H. J., Seong, H. A., Park, K., et al. (2004a) Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol. Endocrinol. 18, 776-790 https://doi.org/10.1210/me.2003-0311
  20. Kim, J. Y., Kim, H. J., Kim, K. T., Park, Y. Y., Seong, H. A., et al. (2004b) Orphan nuclear receptor SHP represses Hepatocyte Nuclear Factor 3 (HNF3)/ Foxa transactivation via inhibition of its DNA binding. Mol. Endocrinol. 18, 2880-2894 https://doi.org/10.1210/me.2004-0211
  21. Lee, Y. K. and Moore, D. D. (2002) Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner. J. Biol. Chem. 277, 2463-2467 https://doi.org/10.1074/jbc.M105161200
  22. Lee, Y. K., Dell, H., Dowhan, D. H., Hadzopoulou-Cladaras, M., and Moore, D. D. (2000) The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression. Mol. Cell. Biol. 20, 187-195 https://doi.org/10.1128/MCB.20.1.187-195.2000
  23. Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., et al. (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6, 507-515 https://doi.org/10.1016/S1097-2765(00)00050-2
  24. Maglich, J. M., Caravella, J. A., Lambert, M. H., Willson, T. M., Moore, J. T., et al. (2003) The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily. Nucleic Acids Res. 31, 4051-4058 https://doi.org/10.1093/nar/gkg444
  25. Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., et al. (1994) Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature 372, 672–676
  26. Nishigori, H., Tomura, H., Tonooka, N., Kanamori, M., Yamada, S., et al. (2001) Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc. Natl. Acad. Sci. USA 98, 575-580
  27. Park, Y. Y., Kim, H. J., Kim, J. Y., Kim, M. Y., Song, K. H., et al. (2004) Differential role of the loop region between helices H6 and H7 within the orphan nuclear receptors small heterodimer partner and DAX-1. Mol. Endocrinol. 18, 1082-1095 https://doi.org/10.1210/me.2003-0339
  28. Robinson-Rechavi, M., Carpentier, A.-S., Duffraisse, M., and Laudet, V. (2001). How many nuclear hormone receptors in the human genome? Trends Genet. 17, 554-556 https://doi.org/10.1016/S0168-9525(01)02417-9
  29. Sanyal, S., Kim, J. Y., Kim, H. J., Takeda, J., Lee, Y. K., et al. (2002) Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms. J. Biol. Chem. 277, 1739-1748 https://doi.org/10.1074/jbc.M106140200
  30. Seol, W., Choi, H. S., and Moore, D. D. (1996) An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science 272, 1336-1339 https://doi.org/10.1126/science.272.5266.1336
  31. Seol, W., Chung, M., and Moore, D. D. (1997) Novel receptor interaction and repression domains in the orphan receptor SHP. Mol. Cell. Biol. 17, 7126-7131 https://doi.org/10.1128/MCB.17.12.7126
  32. Sluder, A. E. and Maina, C. V. (2001). Nuclear receptors in nematodes: Themes and variations. Trends Genet. 17, 206-213 https://doi.org/10.1016/S0168-9525(01)02242-9
  33. Song, K. H., Park, Y. Y., Park, K., Hong, C. Y., Park, J. H., et al. (2004) The atypical orphan nuclear receptor DAX-1 interacts with orphan nuclear receptor Nur77 and represses its transactivation. Mol. Endocrinol. 18, 1929-1940 https://doi.org/10.1210/me.2004-0043
  34. Sugita, J., Takase, M., and Nakamura, M. (2001) Expression of Dax-1 during gonadal development of the frog. Gene 280, 67-74 https://doi.org/10.1016/S0378-1119(01)00739-9
  35. Suzuki, T., Kasahara, M., Yoshioka, H., Morohashi, K., and Umesono, K. (2003) LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Mol. Cell. Biol. 23, 238-249 https://doi.org/10.1128/MCB.23.1.238-249.2003
  36. Tomita, A., Buchholz, D. R., and Shi, Y. B. (2004) Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development. Mol. Cell. Biol. 24, 3337-3346 https://doi.org/10.1128/MCB.24.8.3337-3346.2004
  37. Wang, Z. J., Jeffs, B., Ito, M., Achermann, J. C., Yu, R. N., et al. (2001) Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1. Proc. Natl. Acad. Sci. USA 98, 7988-7993
  38. Wang, D. S., Kobayashi, T., Senthilkumaran, B., Sakai, F., Sudhakumari, C. C., et al. (2002) Molecular cloning of DAX1 and SHP cDNAs and their expression patterns in the Nile tilapia, Oreochromis niloticus. Biochem. Biophys. Res. Commun. 297, 632-640 https://doi.org/10.1016/S0006-291X(02)02252-0
  39. Yoshiura, Y., Senthilkumaran, B., Watanabe, M., Oba, Y., Kobayashi, T., et al. (2003) Synergistic expression of Ad4BP/SF-1 and cytochrome P-450 aromatase (ovarian type) in the ovary of Nile tilapia, Oreochromis niloticus, during vitellogenesis suggests transcriptional interaction. Biol. Reprod. 68, 1545-1553 https://doi.org/10.1095/biolreprod.102.010843
  40. Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., et al. (1994) An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature 372, 635–641
  41. Zhang, H., Thomsen, J. S., Johansson, L., Gustafsson, J. A., and Treuter, E. (2000) DAX-1 functions as an LXXLLcontaining corepressor for activated estrogen receptors. J. Biol. Chem. 275, 39855-39859 https://doi.org/10.1074/jbc.C000567200